Metabolic control of signalling pathways and metabolic auto-regulation

Biology of the Cell

Volumn 107, Issue 8, 2015, Pages 251-272

  Lorendeau, Doriane ^a,b   Christen, Stefan ^a,b   Rinaldi, Gianmarco ^a,b   Fendt, Sarah Maria ^a,b  

^a DEPARTMENT OF PLANT SYSTEMS BIOLOGY   (Belgium)

^b UNIVERSITY OF LEUVEN   (Belgium)

Author keywords

Cancer metabolism; Mass action kinetics; Metabolic regulation; Post translational modifications; Signaling pathways

Indexed keywords

2 OXOGLUTARIC ACID; ADENOSINE TRIPHOSPHATE; ADENOSINE TRIPHOSPHATE CITRATE SYNTHASE; ARGININE; FATTY ACID; GLUTAMINE; HYDROXYMETHYLGLUTARYL COENZYME A REDUCTASE KINASE; HYPOXIA INDUCIBLE FACTOR 1ALPHA; IMMUNOGLOBULIN ENHANCER BINDING PROTEIN; LEUCINE; MALATE DEHYDROGENASE; MAMMALIAN TARGET OF RAPAMYCIN; MAMMALIAN TARGET OF RAPAMYCIN COMPLEX 1; MAMMALIAN TARGET OF RAPAMYCIN COMPLEX 2; NITRIC OXIDE; PROTEIN KINASE B; PROTEIN P53; PYRUVIC ACID; SERINE; STEROL REGULATORY ELEMENT BINDING PROTEIN 1; TRANSCRIPTION FACTOR NRF2;

APOPTOSIS; AUTOREGULATION; BIOSYNTHESIS; BREATHING; CARBON SOURCE; CATABOLISM; CELL AGING; CELL CYCLE ARREST; CELL METABOLISM; CHEMICAL MODIFICATION; CITRIC ACID CYCLE; ENZYME ACTIVITY; FEEDBACK SYSTEM; GLUCOSE METABOLISM; GLYCOLYSIS; GLYCOSYLATION; HUMAN; LIPID METABOLISM; LYSOSOME; METABOLIC REGULATION; NONHUMAN; PRIORITY JOURNAL; PROTEIN EXPRESSION; RESPIRATORY CHAIN; REVIEW; SIGNAL TRANSDUCTION; TRANSCRIPTION REGULATION; ANIMAL; GENE EXPRESSION REGULATION; METABOLISM; PROTEIN PROCESSING;

MAMMALIA;

ANIMALS; GENE EXPRESSION REGULATION; HUMANS; METABOLIC NETWORKS AND PATHWAYS; PROTEIN PROCESSING, POST-TRANSLATIONAL; SIGNAL TRANSDUCTION;

EID: 84938555849     PISSN: 02484900     EISSN: 1768322X     Source Type: Journal    
DOI: 10.1111/boc.201500015     Document Type: Review

References (263)

1. Acin-Perez, R., Carrascoso, I., Baixauli, F., Roche-Molina, M., Latorre-Pellicer, A., Fernandez-Silva, P., Mittelbrunn, M., Sanchez-Madrid, F., Perez-Martos, A., Lowell, C.A., Manfredi, G. and Enriquez, J.A. (2014) ROS-triggered phosphorylation of complex II by Fgr kinase regulates cellular adaptation to fuel use. Cell Metab. 19, 1020-33
2. Adam, J., Yang, M., Soga, T. and Pollard, P.J. (2014) Rare insights into cancer biology. Oncogene 33, 2547-2556
3. Ahn, B.H., Kim, H.S., Song, S., Lee, I.H., Liu, J., Vassilopoulos, A., Deng, C.X. and Finkel, T. (2008) A role for the mitochondrial deacetylase Sirt3 in regulating energy homeostasis. Proc. Natl. Acad. Sci. U.S.A. 105, 14447-14452
4. Alderson, N.L., Wang, Y., Blatnik, M., Frizzell, N., Walla, M.D., Lyons, T.J., Alt, N., Carson, J.A., Nagai, R., Thorpe, S.R. and Baynes, J.W. (2006) S-(2-Succinyl)cysteine: a novel chemical modification of tissue proteins by a Krebs cycle intermediate. Arch. Biochem. Biophys. 450, 1-8
5. Ananieva, E.A., Patel, C.H., Drake, C.H., Powell, J.D. and Hutson, S.M. (2014) Cytosolic branched chain aminotransferase (BCATc) regulates mTORC1 signaling and glycolytic metabolism in CD4+ T cells. J. Biol. Chem. 289, 18793-18804
6. Anastasiou, D., Poulogiannis, G., Asara, J.M., Boxer, M.B., Jiang, J.K., Shen, M., Bellinger, G., Sasaki, A.T., Locasale, J.W., Auld, D.S., Thomas, C.J., Vander Heiden, M.G. and Cantley, L.C. (2011) Inhibition of pyruvate kinase M2 by reactive oxygen species contributes to cellular antioxidant responses. Science 334, 1278-1283
7. Applegate, M.A., Humphries, K.M. and Szweda, L.I. (2008) Reversible inhibition of alpha-ketoglutarate dehydrogenase by hydrogen peroxide: glutathionylation and protection of lipoic acid. Biochemistry 47, 473-478
8. Aroor, A.R., Mandavia, C.H. and Sowers, J.R. (2012) Insulin resistance and heart failure: molecular mechanisms. Heart Fail. Clin. 8, 609-617
9. Avezov, K., Reznick, A.Z. and Aizenbud, D. (2014) LDH enzyme activity in human saliva: the effect of exposure to cigarette smoke and its different components. Arch. Oral Biol. 59, 142-148
10. Bardella, C., Olivero, M., Lorenzato, A., Geuna, M., Adam, J., O'Flaherty, L., Rustin, P., Tomlinson, I., Pollard, P.J. and Di Renzo, M.F. (2012) Cells lacking the fumarase tumor suppressor are protected from apoptosis through a hypoxia-inducible factor-independent, AMPK-dependent mechanism. Mol. Cell. Biol. 32, 3081-3094
11. Ben-Sahra, I., Howell, J.J., Asara, J.M. and Manning, B.D. (2013) Stimulation of de novo pyrimidine synthesis by growth signaling through mTOR and S6K1. Science 339, 1323-1328
12. Berkers, C.R., Maddocks, O.D., Cheung, E.C., Mor, I. and Vousden, K.H. (2013) Metabolic regulation by p53 family members. Cell Metab. 18, 617-633
13. Billiard, J., Dennison, J.B., Briand, J., Annan, R.S., Chai, D., Colon, M., Dodson, C.S., Gilbert, S.A., Greshock, J., Jing, J., Lu, H., McSurdy-Freed, J.E., Orband-Miller, L.A., Mills, G.B., Quinn, C.J., Schneck, J.L., Scott, G.F., Shaw, A.N., Waitt, G.M., Wooster, R.F. and Duffy, K.J. (2013) Quinoline 3-sulfonamides inhibit lactate dehydrogenase A and reverse aerobic glycolysis in cancer cells. Cancer Metab. 1, 19
14. Blatnik, M., Frizzell, N., Thorpe, S.R. and Baynes, J.W. (2008) Inactivation of glyceraldehyde-3-phosphate dehydrogenase by fumarate in diabetes: formation of S-(2-succinyl)cysteine, a novel chemical modification of protein and possible biomarker of mitochondrial stress. Diabetes 57, 41-49
15. Blommaart, E.F., Luiken, J.J., Blommaart, P.J., van Woerkom, G.M. and Meijer, A.J. (1995) Phosphorylation of ribosomal protein S6 is inhibitory for autophagy in isolated rat hepatocytes. J. Biol. Chem. 270, 2320-2326
16. Butera, P.C., Willard, D.M. and Raymond, S.A. (1992) Effects of PVN lesions on the responsiveness of female rats to estradiol. Brain Res. 576, 304-310
17. Cahuana, G.M., Tejedo, J.R., Jimenez, J., Ramirez, R., Sobrino, F. and Bedoya, F.J. (2004) Nitric oxide-induced carbonylation of Bcl-2, GAPDH and ANT precedes apoptotic events in insulin-secreting RINm5F cells. Exp. Cell Res. 293, 22-30
18. Cantor, J.R. and Sabatini, D.M. (2012) Cancer cell metabolism: one hallmark, many faces. Cancer Discov. 2, 881-898
19. Cardaci, S., Filomeni, G. and Ciriolo, M.R. (2012) Redox implications of AMPK-mediated signal transduction beyond energetic clues. J. Cell Sci. 125, 2115-2125
20. Carling, D., Clarke, P.R., Zammit, V.A. and Hardie, D.G. (1989) Purification and characterization of the AMP-activated protein kinase. Copurification of acetyl-CoA carboxylase kinase and 3-hydroxy-3-methylglutaryl-CoA reductase kinase activities. Eur. J. Biochem. 186, 129-136
21. Carrer, A. and Wellen, K.E. (2014) Metabolism and epigenetics: a link cancer cells exploit. Curr. Opin. Biotechnol. 34C, 23-29
22. Chaneton, B., Hillmann, P., Zheng, L., Martin, A.C., Maddocks, O.D., Chokkathukalam, A., Coyle, J.E., Jankevics, A., Holding, F.P., Vousden, K.H., Frezza, C., O'Reilly, M. and Gottlieb, E. (2012) Serine is a natural ligand and allosteric activator of pyruvate kinase M2. Nature 491, 458-462
23. Chang, C.F., Diers, A.R. and Hogg, N. (2015) Cancer cell metabolism and the modulating effects of nitric oxide. Free Radic Biol Med 79, 324-336
24. Chen, L., Wang, J., Zhang, Y.Y., Yan, S.F., Neumann, D., Schlattner, U., Wang, Z.X. and Wu, J.W. (2012) AMP-activated protein kinase undergoes nucleotide-dependent conformational changes. Nat. Struct. Mol. Biol. 19, 716-718
25. Chen, Y., Rodrik, V. and Foster, D.A. (2005) Alternative phospholipase D/mTOR survival signal in human breast cancer cells. Oncogene 24, 672-679
26. Chen, Y., Zheng, Y. and Foster, D.A. (2003) Phospholipase D confers rapamycin resistance in human breast cancer cells. Oncogene 22, 3937-3942
27. Chen, Y.R., Chen, C.L., Pfeiffer, D.R. and Zweier, J.L. (2007) Mitochondrial complex II in the post-ischemic heart: oxidative injury and the role of protein S-glutathionylation. J. Biol. Chem. 282, 32640-32654
28. Chen, Z.P., McConell, G.K., Michell, B.J., Snow, R.J., Canny, B.J. and Kemp, B.E. (2000) AMPK signaling in contracting human skeletal muscle: acetyl-CoA carboxylase and NO synthase phosphorylation. Am. J. Physiol. Endocrinol. Metab. 279, E1202-E1206
29. Chin, R.M., Fu, X., Pai, M.Y., Vergnes, L., Hwang, H., Deng, G., Diep, S., Lomenick, B., Meli, V.S., Monsalve, G.C., Hu, E., Whelan, S.A., Wang, J.X., Jung, G., Solis, G.M., Fazlollahi, F., Kaweeteerawat, C., Quach, A., Nili, M., Krall, A.S., Godwin, H.A., Chang, H.R., Faull, K.F., Guo, F., Jiang, M., Trauger, S.A., Saghatelian, A., Braas, D., Christofk, H.R., Clarke, C.F., Teitell, M.A., Petrascheck, M., Reue, K., Jung, M.E., Frand, A.R. and Huang, J. (2014) The metabolite alpha-ketoglutarate extends lifespan by inhibiting ATP synthase and TOR. Nature 510, 397-401
30. Choudhary, C., Weinert, B.T., Nishida, Y., Verdin, E. and Mann, M. (2014) The growing landscape of lysine acetylation links metabolism and cell signalling. Nat. Rev. Mol. Cell Biol. 15, 536-550
31. Cimen, H., Han, M.J., Yang, Y., Tong, Q., Koc, H. and Koc, E.C. (2010) Regulation of succinate dehydrogenase activity by SIRT3 in mammalian mitochondria. Biochemistry 49, 304-311
32. Colombo, S.L., Palacios-Callender, M., Frakich, N., Carcamo, S., Kovacs, I., Tudzarova, S. and Moncada, S. (2011) Molecular basis for the differential use of glucose and glutamine in cell proliferation as revealed by synchronized HeLa cells. Proc. Natl. Acad. Sci. U.S.A. 108, 21069-21074
33. Corcoran, C.A., Huang, Y. and Sheikh, M.S. (2006) The regulation of energy generating metabolic pathways by p53. Cancer Biol. Ther. 5, 1610-1613
34. Curtis, J.M., Hahn, W.S., Long, E.K., Burrill, J.S., Arriaga, E.A. and Bernlohr, D.A. (2012) Protein carbonylation and metabolic control systems. Trends Endocrinol. Metab. 23, 399-406
35. Czernin, J. and Phelps, M.E. (2002) Positron emission tomography scanning: current and future applications. Annu. Rev. Med. 53, 89-112
36. deBie, P. and Ciechanover, A. (2011) Ubiquitination of E3 ligases: self-regulation of the ubiquitin system via proteolytic and non-proteolytic mechanisms. Cell Death Differ. 18, 1393-1402
37. DeBock, K., Georgiadou, M. and Carmeliet, P. (2013) Role of endothelial cell metabolism in vessel sprouting. Cell Metab. 18, 634-647
38. Deen, P.M. and Robben, J.H. (2011) Succinate receptors in the kidney. J. Am. Soc. Nephrol. 22, 1416-1422
39. Dell' Antone, P. (2012) Energy metabolism in cancer cells: how to explain the Warburg and Crabtree effects? Med. Hypotheses 79, 388-392
40. Dennis, P.B., Jaeschke, A., Saitoh, M., Fowler, B., Kozma, S.C. and Thomas, G. (2001) Mammalian TOR: a homeostatic ATP sensor. Science 294, 1102-1105
41. Denton, R.M. and Randle, P.J. (1966) Citrate and the regulation of adipose-tissue phosphofructokinase. Biochem. J. 100, 420-423
42. Denzel, M.S. and Antebi, A. (2014) Hexosamine pathway and (ER) protein quality control. Curr. Opin. Cell Biol. 33C, 14-18
43. Diaz-Ruiz, R., Rigoulet, M. and Devin, A. (2011) The Warburg and Crabtree effects: on the origin of cancer cell energy metabolism and of yeast glucose repression. Biochim. Biophys. Acta 1807, 568-576
44. Dimmeler, S., Lottspeich, F. and Brune, B. (1992) Nitric oxide causes ADP-ribosylation and inhibition of glyceraldehyde-3-phosphate dehydrogenase. J. Biol. Chem. 267, 16771-16774
45. Doherty, J.R., Yang, C., Scott, K.E., Cameron, M.D., Fallahi, M., Li, W., Hall, M.A., Amelio, A.L., Mishra, J.K., Li, F., Tortosa, M., Genau, H.M., Rounbehler, R.J., Lu, Y., Dang, C.V., Kumar, K.G., Butler, A.A., Bannister, T.D., Hooper, A.T., Unsal-Kacmaz, K., Roush, W.R. and Cleveland, J.L. (2014) Blocking lactate export by inhibiting the Myc target MCT1 Disables glycolysis and glutathione synthesis. Cancer Res. 74, 908-920
46. Dolfi, S.C., Chan, L.L., Qiu, J., Tedeschi, P.M., Bertino, J.R., Hirshfield, K.M., Oltvai, Z.N. and Vazquez, A. (2013) The metabolic demands of cancer cells are coupled to their size and protein synthesis rates. Cancer Metab. 1, 20
47. Du, J., Zhou, Y., Su, X., Yu, J.J., Khan, S., Jiang, H., Kim, J., Woo, J., Kim, J.H., Choi, B.H., He, B., Chen, W., Zhang, S., Cerione, R.A., Auwerx, J., Hao, Q. and Lin, H. (2011) Sirt5 is a NAD-dependent protein lysine demalonylase and desuccinylase. Science 334, 806-809
48. Duarte, J.M., Schuck, P.F., Wenk, G.L. and Ferreira, G.C. (2014) Metabolic disturbances in diseases with neurological involvement. Aging Dis. 5, 238-255
49. Duran, R.V., Oppliger, W., Robitaille, A.M., Heiserich, L., Skendaj, R., Gottlieb, E. and Hall, M.N. (2012) Glutaminolysis activates Rag-mTORC1 signaling. Mol. Cell 47, 349-358
50. Fahien, L.A. and Kmiotek, E. (1981) Regulation of glutamate dehydrogenase by palmitoyl-coenzyme A. Arch. Biochem. Biophys. 212, 247-253
51. Fan, J., Hitosugi, T., Chung, T.W., Xie, J., Ge, Q., Gu, T.L., Polakiewicz, R.D., Chen, G.Z., Boggon, T.J., Lonial, S., Khuri, F.R., Kang, S. and Chen, J. (2011) Tyrosine phosphorylation of lactate dehydrogenase A is important for NADH/NAD(+) redox homeostasis in cancer cells. Mol. Cell. Biol. 31, 4938-4950
52. Fang, Y., Vilella-Bach, M., Bachmann, R., Flanigan, A. and Chen, J. (2001) Phosphatidic acid-mediated mitogenic activation of mTOR signaling. Science 294, 1942-1945
53. Fendt, S.M., Bell, E.L., Keibler, M.A., Davidson, S.M., Wirth, G.J., Fiske, B., Mayers, J.R., Schwab, M., Bellinger, G., Csibi, A., Patnaik, A., Blouin, M.J., Cantley, L.C., Guarente, L., Blenis, J., Pollak, M.N., Olumi, A.F., Vander Heiden, M.G. and Stephanopoulos, G. (2013a) Metformin decreases glucose oxidation and increases the dependency of prostate cancer cells on reductive glutamine metabolism. Cancer Res. 73, 4429-4438
54. Fendt, S.M., Bell, E.L., Keibler, M.A., Olenchock, B.A., Mayers, J.R., Wasylenko, T.M., Vokes, N.I., Guarente, L., Vander Heiden, M.G. and Stephanopoulos, G. (2013b) Reductive glutamine metabolism is a function of the alpha-ketoglutarate to citrate ratio in cells. Nat. Commun. 4, 2236
55. Fendt, S.M., Buescher, J.M., Rudroff, F., Picotti, P., Zamboni, N. and Sauer, U. (2010) Tradeoff between enzyme and metabolite efficiency maintains metabolic homeostasis upon perturbations in enzyme capacity. Mol. Syst. Biol. 6, 356
56. Folger, O., Jerby, L., Frezza, C., Gottlieb, E., Ruppin, E. and Shlomi, T. (2011) Predicting selective drug targets in cancer through metabolic networks. Mol. Syst. Biol. 7, 501
57. Fratelli, M., Demol, H., Puype, M., Casagrande, S., Eberini, I., Salmona, M., Bonetto, V., Mengozzi, M., Duffieux, F., Miclet, E., Bachi, A., Vandekerckhove, J., Gianazza, E. and Ghezzi, P. (2002) Identification by redox proteomics of glutathionylated proteins in oxidatively stressed human T lymphocytes. Proc. Natl. Acad. Sci. U.S.A. 99, 3505-3510
58. Gallogly, M.M., Starke, D.W. and Mieyal, J.J. (2009) Mechanistic and kinetic details of catalysis of thiol-disulfide exchange by glutaredoxins and potential mechanisms of regulation. Antioxid. Redox Signal. 11, 1059-1081
59. Gameiro, P.A., Laviolette, L.A., Kelleher, J.K., Iliopoulos, O. and Stephanopoulos, G. (2013a) Cofactor balance by nicotinamide nucleotide transhydrogenase (NNT) coordinates reductive carboxylation and glucose catabolism in the tricarboxylic acid (TCA) cycle. J. Biol. Chem. 288, 12967-12977
60. Gameiro, P.A., Yang, J., Metelo, A.M., Perez-Carro, R., Baker, R., Wang, Z., Arreola, A., Rathmell, W.K., Olumi, A., Lopez-Larrubia, P., Stephanopoulos, G. and Iliopoulos, O. (2013b) In vivo HIF-mediated reductive carboxylation is regulated by citrate levels and sensitizes VHL-deficient cells to glutamine deprivation. Cell Metab. 17, 372-385
61. Garcia, J., Han, D., Sancheti, H., Yap, L.P., Kaplowitz, N. and Cadenas, E. (2010) Regulation of mitochondrial glutathione redox status and protein glutathionylation by respiratory substrates. J. Biol. Chem. 285, 39646-39654
62. Gomes, A.P. and Blenis, J. (2015) A nexus for cellular homeostasis: the interplay between metabolic and signal transduction pathways. Curr. Opin. Biotechnol. 34C, 110-117
63. Gorg, B., Qvartskhava, N., Voss, P., Grune, T., Haussinger, D. and Schliess, F. (2007) Reversible inhibition of mammalian glutamine synthetase by tyrosine nitration. FEBS Lett. 581, 84-90
64. Gowans, G.J., Hawley, S.A., Ross, F.A. and Hardie, D.G. (2013) AMP is a true physiological regulator of AMP-activated protein kinase by both allosteric activation and enhancing net phosphorylation. Cell Metab. 18, 556-566
65. Green, D.R. and Kroemer, G. (2009) Cytoplasmic functions of the tumour suppressor p53. Nature 458, 1127-1130
66. Gui, D.Y., Lewis, C.A. and Vander Heiden, M.G. (2013) Allosteric regulation of PKM2 allows cellular adaptation to different physiological states. Sci. Signal. 6, pe7
67. Gut, P. and Verdin, E. (2013) The nexus of chromatin regulation and intermediary metabolism. Nature 502, 489-498
68. Gwinn, D.M., Asara, J.M. and Shaw, R.J. (2010) Raptor is phosphorylated by cdc2 during mitosis. PLoS One 5, e9197
69. Haigis, M.C., Mostoslavsky, R., Haigis, K.M., Fahie, K., Christodoulou, D.C., Murphy, A.J., Valenzuela, D.M., Yancopoulos, G.D., Karow, M., Blander, G., Wolberger, C., Prolla, T.A., Weindruch, R., Alt, F.W. and Guarente, L. (2006) SIRT4 inhibits glutamate dehydrogenase and opposes the effects of calorie restriction in pancreatic beta cells. Cell 126, 941-954
70. Hallows, W.C., Lee, S. and Denu, J.M. (2006) Sirtuins deacetylate and activate mammalian acetyl-CoA synthetases. Proc. Natl. Acad. Sci. U.S.A. 103, 10230-10235
71. Hallows, W.C., Yu, W. and Denu, J.M. (2012) Regulation of glycolytic enzyme phosphoglycerate mutase-1 by Sirt1 protein-mediated deacetylation. J. Biol. Chem. 287, 3850-3858
72. Hallows, W.C., Yu, W., Smith, B.C., Devries, M.K., Ellinger, J.J., Someya, S., Shortreed, M.R., Prolla, T., Markley, J.L., Smith, L.M., Zhao, S., Guan, K.L. and Denu, J.M. (2011) Sirt3 promotes the urea cycle and fatty acid oxidation during dietary restriction. Mol. Cell 41, 139-149
73. Han, D., Canali, R., Garcia, J., Aguilera, R., Gallaher, T.K. and Cadenas, E. (2005) Sites and mechanisms of aconitase inactivation by peroxynitrite: modulation by citrate and glutathione. Biochemistry 44, 11986-11996
74. Han, J.M., Jeong, S.J., Park, M.C., Kim, G., Kwon, N.H., Kim, H.K., Ha, S.H., Ryu, S.H. and Kim, S. (2012) Leucyl-tRNA synthetase is an intracellular leucine sensor for the mTORC1-signaling pathway. Cell 149, 410-424
75. Han, Z., Zhong, L., Srivastava, A. and Stacpoole, P.W. (2008) Pyruvate dehydrogenase complex deficiency caused by ubiquitination and proteasome-mediated degradation of the E1 subunit. J. Biol. Chem. 283, 237-243
76. Hara, K., Yonezawa, K., Weng, Q.P., Kozlowski, M.T., Belham, C. and Avruch, J. (1998) Amino acid sufficiency and mTOR regulate p70 S6 kinase and eIF-4E BP1 through a common effector mechanism. J. Biol. Chem. 273, 14484-14494
77. Hardie, D.G. (2014) AMPK: positive and negative regulation, and its role in whole-body energy homeostasis. Curr. Opin. Cell Biol. 33C, 1-7
78. Hardie, D.G., Ross, F.A. and Hawley, S.A. (2012) AMPK: a nutrient and energy sensor that maintains energy homeostasis. Nat. Rev. Mol. Cell Biol. 13, 251-262
79. Herrero-Yraola, A., Bakhit, S.M., Franke, P., Weise, C., Schweiger, M., Jorcke, D. and Ziegler, M. (2001) Regulation of glutamate dehydrogenase by reversible ADP-ribosylation in mitochondria. EMBO J. 20, 2404-2412
80. Hinke, S.A., Martens, G.A., Cai, Y., Finsi, J., Heimberg, H., Pipeleers, D. and Vande Casteele, M. (2007) Methyl succinate antagonises biguanide-induced AMPK-activation and death of pancreatic beta-cells through restoration of mitochondrial electron transfer. Br. J. Pharmacol. 150, 1031-1043
81. Hitosugi, T., Kang, S., Vander Heiden, M.G., Chung, T.W., Elf, S., Lythgoe, K., Dong, S., Lonial, S., Wang, X., Chen, G.Z., Xie, J., Gu, T.L., Polakiewicz, R.D., Roesel, J.L., Boggon, T.J., Khuri, F.R., Gilliland, D.G., Cantley, L.C., Kaufman, J. and Chen, J. (2009) Tyrosine phosphorylation inhibits PKM2 to promote the Warburg effect and tumor growth. Sci. Signal. 2, ra73
82. Hitosugi, T., Zhou, L., Elf, S., Fan, J., Kang, H.B., Seo, J.H., Shan, C., Dai, Q., Zhang, L., Xie, J., Gu, T.L., Jin, P., Aleckovic, M., LeRoy, G., Kang, Y., Sudderth, J.A., DeBerardinis, R.J., Luan, C.H., Chen, G.Z., Muller, S., Shin, D.M., Owonikoko, T.K., Lonial, S., Arellano, M.L., Khoury, H.J., Khuri, F.R., Lee, B.H., Ye, K., Boggon, T.J., Kang, S., He, C. and Chen, J. (2012) Phosphoglycerate mutase 1 coordinates glycolysis and biosynthesis to promote tumor growth. Cancer Cell 22, 585-600
83. Hitosugi, T., Zhou, L., Fan, J., Elf, S., Zhang, L., Xie, J., Wang, Y., Gu, T.L., Aleckovic, M., LeRoy, G., Kang, Y., Kang, H.B., Seo, J.H., Shan, C., Jin, P., Gong, W., Lonial, S., Arellano, M.L., Khoury, H.J., Chen, G.Z., Shin, D.M., Khuri, F.R., Boggon, T.J., Kang, S., He, C. and Chen, J. (2013) Tyr26 phosphorylation of PGAM1 provides a metabolic advantage to tumours by stabilizing the active conformation. Nat. Commun. 4, 1790
84. Holbrook, J.J. and Ingram, V.A. (1973) Ionic properties of an essential histidine residue in pig heart lactate dehydrogenase. Biochem. J. 131, 729-738
85. Howell, J.J. and Manning, B.D. (2011) mTOR couples cellular nutrient sensing to organismal metabolic homeostasis. Trends Endocrinol. Metab. 22, 94-102
86. Huang, K. and Fingar, D.C. (2014) Growing knowledge of the mTOR signaling network. Semin. Cell Dev. Biol. 36C, 79-90
87. Huang, Z., Ichihara, S., Oikawa, S., Chang, J., Zhang, L., Subramanian, K., Mohideen, S.S. and Ichihara, G. (2012) Proteomic identification of carbonylated proteins in F344 rat hippocampus after 1-bromopropane exposure. Toxicol. Appl. Pharmacol. 263, 44-52
88. Humphries, K.M. and Szweda, L.I. (1998) Selective inactivation of alpha-ketoglutarate dehydrogenase and pyruvate dehydrogenase: reaction of lipoic acid with 4-hydroxy-2-nonenal. Biochemistry 37, 15835-15841
89. Humphries, K.M., Yoo, Y. and Szweda, L.I. (1998) Inhibition of NADH-linked mitochondrial respiration by 4-hydroxy-2-nonenal. Biochemistry 37, 552-557
90. Hurd, T.R., Requejo, R., Filipovska, A., Brown, S., Prime, T.A., Robinson, A.J., Fearnley, I.M. and Murphy, M.P. (2008) Complex I within oxidatively stressed bovine heart mitochondria is glutathionylated on Cys-531 and Cys-704 of the 75-kDa subunit: potential role of CYS residues in decreasing oxidative damage. J. Biol. Chem. 283, 24801-24815
91. Ikeda, Y., Tanaka, T. and Noguchi, T. (1997) Conversion of non-allosteric pyruvate kinase isozyme into an allosteric enzyme by a single amino acid substitution. J. Biol. Chem. 272, 20495-20501
92. Inoki, K., Ouyang, H., Zhu, T., Lindvall, C., Wang, Y., Zhang, X., Yang, Q., Bennett, C., Harada, Y., Stankunas, K., Wang, C.Y., He, X., MacDougald, O.A., You, M., Williams, B.O. and Guan, K.L. (2006) TSC2 integrates Wnt and energy signals via a coordinated phosphorylation by AMPK and GSK3 to regulate cell growth. Cell 126, 955-968
93. Inoki, K., Zhu, T. and Guan, K.L. (2003) TSC2 mediates cellular energy response to control cell growth and survival. Cell 115, 577-590
94. Israelsen, W.J., Dayton, T.L., Davidson, S.M., Fiske, B.P., Hosios, A.M., Bellinger, G., Li, J., Yu, Y., Sasaki, M., Horner, J.W., Burga, L.N., Xie, J., Jurczak, M.J., DePinho, R.A., Clish, C.B., Jacks, T., Kibbey, R.G., Wulf, G.M., Di Vizio, D., Mills, G.B., Cantley, L.C. and Vander Heiden, M.G. (2013) PKM2 isoform-specific deletion reveals a differential requirement for pyruvate kinase in tumor cells. Cell 155, 397-409
95. Jenkins, C.M., Yang, J., Sims, H.F. and Gross, R.W. (2011) Reversible high affinity inhibition of phosphofructokinase-1 by acyl-CoA: a mechanism integrating glycolytic flux with lipid metabolism. J. Biol. Chem. 286, 11937-11950
96. Jewell, J.L., Kim, Y.C., Russell, R.C., Yu, F.X., Park, H.W., Plouffe, S.W., Tagliabracci, V.S. and Guan, K.L. (2015) Metabolism. Differential regulation of mTORC1 by leucine and glutamine. Science 347(6218), 194-198
97. Jewell, J.L., Russell, R.C. and Guan, K.L. (2013) Amino acid signalling upstream of mTOR. Nat. Rev. Mol. Cell Biol. 14, 133-139
98. Jiang, P., Du, W., Mancuso, A., Wellen, K.E. and Yang, X. (2013) Reciprocal regulation of p53 and malic enzymes modulates metabolism and senescence. Nature 493, 689-693
99. Jiang, W., Wang, S., Xiao, M., Lin, Y., Zhou, L., Lei, Q., Xiong, Y., Guan, K.L. and Zhao, S. (2011) Acetylation regulates gluconeogenesis by promoting PEPCK1 degradation via recruiting the UBR5 ubiquitin ligase. Mol. Cell 43, 33-44
100. Jing, E., O'Neill, B.T., Rardin, M.J., Kleinridders, A., Ilkeyeva, O.R., Ussar, S., Bain, J.R., Lee, K.Y., Verdin, E.M., Newgard, C.B., Gibson, B.W. and Kahn, C.R. (2013) Sirt3 regulates metabolic flexibility of skeletal muscle through reversible enzymatic deacetylation. Diabetes 62, 3404-3417
101. Jones, R.G., Plas, D.R., Kubek, S., Buzzai, M., Mu, J., Xu, Y., Birnbaum, M.J. and Thompson, C.B. (2005) AMP-activated protein kinase induces a p53-dependent metabolic checkpoint. Mol. Cell 18, 283-293
102. Jose, C., Bellance, N. and Rossignol, R. (2011) Choosing between glycolysis and oxidative phosphorylation: a tumor's dilemma? Biochim. Biophys. Acta 1807, 552-561
103. Jozwiak, P., Forma, E., Brys, M. and Krzeslak, A. (2014) O-GlcNAcylation and Metabolic Reprograming in Cancer. Front. Endocrinol. (Lausanne) 5, 145
104. Kaelin, W.G., Jr. and McKnight, S.L. (2013) Influence of metabolism on epigenetics and disease. Cell 153, 56-69
105. Kagimoto, T. and Uyeda, K. (1979) Hormone-stimulated phosphorylation of liver phosphofructokinase in vivo. J. Biol. Chem. 254, 5584-5587
106. Kahn, S.E., Hull, R.L. and Utzschneider, K.M. (2006) Mechanisms linking obesity to insulin resistance and type 2 diabetes. Nature 444, 840-846
107. Karamanlidis, G., Lee, C.F., Garcia-Menendez, L., Kolwicz, S.C., Jr., Suthammarak, W., Gong, G., Sedensky, M.M., Morgan, P.G., Wang, W. and Tian, R. (2013) Mitochondrial complex I deficiency increases protein acetylation and accelerates heart failure. Cell Metab. 18, 239-250
108. Kawauchi, K., Araki, K., Tobiume, K. and Tanaka, N. (2009) Loss of p53 enhances catalytic activity of IKKbeta through O-linked beta-N-acetyl glucosamine modification. Proc. Natl. Acad. Sci. U.S.A. 106, 3431-3436
109. Kim, E.Y., Han, B.S., Kim, W.K., Lee, S.C. and Bae, K.H. (2013a) Acceleration of adipogenic differentiation via acetylation of malate dehydrogenase 2. Biochem. Biophys. Res. Commun. 441, 77-82
110. Kim, K.H., Lopez-Casillas, F., Bai, D.H., Luo, X. and Pape, M.E. (1989) Role of reversible phosphorylation of acetyl-CoA carboxylase in long-chain fatty acid synthesis. FASEB J. 3, 2250-2256
111. Kim, S.G., Buel, G.R. and Blenis, J. (2013b) Nutrient regulation of the mTOR complex 1 signaling pathway. Mol. Cells 35, 463-473
112. Kim, S.G., Hoffman, G.R., Poulogiannis, G., Buel, G.R., Jang, Y.J., Lee, K.W., Kim, B.Y., Erikson, R.L., Cantley, L.C., Choo, A.Y. and Blenis, J. (2013c) Metabolic stress controls mTORC1 lysosomal localization and dimerization by regulating the TTT-RUVBL1/2 complex. Mol. Cell 49, 172-185
113. Kimura, Y. and Tanaka, K. (2010) Regulatory mechanisms involved in the control of ubiquitin homeostasis. J. Biochem. 147, 793-798
114. Klaus, A., Polge, C., Zorman, S., Auchli, Y., Brunisholz, R. and Schlattner, U. (2012) A two-dimensional screen for AMPK substrates identifies tumor suppressor fumarate hydratase as a preferential AMPKalpha2 substrate. J. Proteomics 75, 3304-3313
115. Kochanowski, K., Volkmer, B., Gerosa, L., Haverkorn van Rijsewijk, B.R., Schmidt, A. and Heinemann, M. (2013) Functioning of a metabolic flux sensor in Escherichia coli. Proc. Natl. Acad. Sci. U.S.A. 110, 1130-1135
116. Komander, D. and Rape, M. (2012) The ubiquitin code. Annu. Rev. Biochem. 81, 203-229
117. Kwong, J.Q., Beal, M.F. and Manfredi, G. (2006) The role of mitochondria in inherited neurodegenerative diseases. J. Neurochem. 97, 1659-1675
118. Laplante, M. and Sabatini, D.M. (2012) mTOR signaling in growth control and disease. Cell 149, 274-293
119. Lau, A.W., Liu, P., Inuzuka, H. and Gao, D. (2014) SIRT1 phosphorylation by AMP-activated protein kinase regulates p53 acetylation. Am. J. Cancer Res. 4, 245-255
120. Laurent, G., German, N.J., Saha, A.K., de Boer, V.C., Davies, M., Koves, T.R., Dephoure, N., Fischer, F., Boanca, G., Vaitheesvaran, B., Lovitch, S.B., Sharpe, A.H., Kurland, I.J., Steegborn, C., Gygi, S.P., Muoio, D.M., Ruderman, N.B. and Haigis, M.C. (2013) SIRT4 coordinates the balance between lipid synthesis and catabolism by repressing malonyl CoA decarboxylase. Mol. Cell 50, 686-698
121. Lee, C.W., Wong, L.L., Tse, E.Y., Liu, H.F., Leong, V.Y., Lee, J.M., Hardie, D.G., Ng, I.O. and Ching, Y.P. (2012) AMPK promotes p53 acetylation via phosphorylation and inactivation of SIRT1 in liver cancer cells. Cancer Res. 72, 4394-404
122. Lee, J.V., Carrer, A., Shah, S., Snyder, N.W., Wei, S., Venneti, S., Worth, A.J., Yuan, Z.F., Lim, H.W., Liu, S., Jackson, E., Aiello, N.M., Haas, N.B., Rebbeck, T.R., Judkins, A., Won, K.J., Chodosh, L.A., Garcia, B.A., Stanger, B.Z., Feldman, M.D., Blair, I.A. and Wellen, K.E. (2014) Akt-dependent metabolic reprogramming regulates tumor cell histone acetylation. Cell Metab. 20, 306-319
123. Lee, S.M., Kim, J.H., Cho, E.J. and Youn, H.D. (2009) A nucleocytoplasmic malate dehydrogenase regulates p53 transcriptional activity in response to metabolic stress. Cell Death Differ. 16, 738-748
124. Lee, W.H., Choi, J.S., Byun, M.R., Koo, K.T., Shin, S., Lee, S.K. and Surh, Y.J. (2010) Functional inactivation of triosephosphate isomerase through phosphorylation during etoposide-induced apoptosis in HeLa cells: potential role of Cdk2. Toxicology 278, 224-228
125. Lewis, C.A., Parker, S.J., Fiske, B.P., McCloskey, D., Gui, D.Y., Green, C.R., Vokes, N.I., Feist, A.M., Vander Heiden, M.G. and Metallo, C.M. (2014) Tracing compartmentalized NADPH metabolism in the cytosol and mitochondria of mammalian cells. Mol. Cell 55, 253-263
126. Li, L., Chen, Y. and Gibson, S.B. (2013) Starvation-induced autophagy is regulated by mitochondrial reactive oxygen species leading to AMPK activation. Cell Signal. 25, 50-65
127. Liang, B., Guo, Z., Xie, F. and Zhao, A. (2013) Antihyperglycemic and antihyperlipidemic activities of aqueous extract of Hericium erinaceus in experimental diabetic rats. BMC Complement Altern. Med. 13, 253
128. Lii, C.K., Lin, A.H., Lee, S.L., Chen, H.W. and Wang, T.S. (2011) Oxidative modifications of proteins by sodium arsenite in human umbilical vein endothelial cells. Environ. Toxicol. 26, 459-471
129. Lin, R., Tao, R., Gao, X., Li, T., Zhou, X., Guan, K.L., Xiong, Y. and Lei, Q.Y. (2013) Acetylation stabilizes ATP-citrate lyase to promote lipid biosynthesis and tumor growth. Mol. Cell 51, 506-518
130. Lind, C., Gerdes, R., Schuppe-Koistinen, I. and Cotgreave, I.A. (1998) Studies on the mechanism of oxidative modification of human glyceraldehyde-3-phosphate dehydrogenase by glutathione: catalysis by glutaredoxin. Biochem. Biophys. Res. Commun. 247, 481-486
131. Link, H., Kochanowski, K. and Sauer, U. (2013) Systematic identification of allosteric protein-metabolite interactions that control enzyme activity in vivo. Nat. Biotechnol. 31, 357-361
132. Linke, S.P., Clarkin, K.C., Di Leonardo, A., Tsou, A. and Wahl, G.M. (1996) A reversible, p53-dependent G0/G1 cell cycle arrest induced by ribonucleotide depletion in the absence of detectable DNA damage. Genes Dev. 10, 934-947
133. Linker, W., Loffler, M. and Schneider, F. (1985) Uridine, but not cytidine can sustain growth of Ehrlich ascites tumor cells in glucose-deprived medium with altered proliferation kinetics. Eur. J. Cell Biol. 36, 176-181
134. Linn, T.C., Pettit, F.H. and Reed, L.J. (1969) Alpha-keto acid dehydrogenase complexes. X. Regulation of the activity of the pyruvate dehydrogenase complex from beef kidney mitochondria by phosphorylation and dephosphorylation. Proc. Natl. Acad. Sci. U.S.A. 62, 234-241
135. Liu, B., Chen, Y. and St. Clair, D.K. (2008) ROS and p53: versatile partnership. Free Radic. Biol. Med. 44, 1529-1535
136. Liu, Q., Simpson, D.C. and Gronert, S. (2013) Carbonylation of mitochondrial aconitase with 4-hydroxy-2-(E)-nonenal: localization and relative reactivity of addition sites. Biochim. Biophys. Acta 1834, 1144-1154
137. Livnat-Levanon, N. and Glickman, M.H. (2011) Ubiquitin-proteasome system and mitochondria-reciprocity. Biochim. Biophys. Acta 1809, 80-87
138. Lo, S.C. and Hannink, M. (2006) PGAM5, a Bcl-XL-interacting protein, is a novel substrate for the redox-regulated Keap1-dependent ubiquitin ligase complex. J. Biol. Chem. 281, 37893-37903
139. Lunt, S.Y., Muralidhar, V., Hosios, A.M., Israelsen, W.J., Gui, D.Y., Newhouse, L., Ogrodzinski, M., Hecht, V., Xu, K., Acevedo, P.N., Hollern, D.P., Bellinger, G., Dayton, T.L., Christen, S., Elia, I., Dinh, A.T., Stephanopoulos, G., Manalis, S.R., Yaffe, M.B., Andrechek, E.R., Fendt, S. and Vander Heiden, M.G. (2015) Pyruvate kinase isoform expression alters nucleotide synthesis to impact cell proliferation. Mol. Cell 57, 95-107
140. Lunt, S.Y. and Vander Heiden, M.G. (2011) Aerobic glycolysis: meeting the metabolic requirements of cell proliferation. Annu. Rev. Cell Dev. Biol. 27, 441-464
141. Luo, W. and Semenza, G.L. (2011) Pyruvate kinase M2 regulates glucose metabolism by functioning as a coactivator for hypoxia-inducible factor 1 in cancer cells. Oncotarget 2, 551-556
142. Lushchak, O.V., Piroddi, M., Galli, F. and Lushchak, V.I. (2014) Aconitase post-translational modification as a key in linkage between Krebs cycle, iron homeostasis, redox signaling, and metabolism of reactive oxygen species. Redox Rep. 19, 8-15
143. Lv, L., Xu, Y.P., Zhao, D., Li, F.L., Wang, W., Sasaki, N., Jiang, Y., Zhou, X., Li, T.T., Guan, K.L., Lei, Q.Y. and Xiong, Y. (2013) Mitogenic and oncogenic stimulation of K433 acetylation promotes PKM2 protein kinase activity and nuclear localization. Mol. Cell 52, 340-352
144. Ma, X.M. and Blenis, J. (2009) Molecular mechanisms of mTOR-mediated translational control. Nat. Rev. Mol. Cell Biol. 10, 307-318
145. Maddocks, O.D., Berkers, C.R., Mason, S.M., Zheng, L., Blyth, K., Gottlieb, E. and Vousden, K.H. (2013) Serine starvation induces stress and p53-dependent metabolic remodelling in cancer cells. Nature 493, 542-546
146. Mailloux, R.J. and Willmore, W.G. (2014) S-glutathionylation reactions in mitochondrial function and disease. Front. Cell Dev. Biol. 2, 68
147. Mannervik, B. and Axelsson, K. (1980) Role of cytoplasmic thioltransferase in cellular regulation by thiol-disulphide interchange. Biochem. J. 190, 125-130
148. Marino, G., Pietrocola, F., Eisenberg, T., Kong, Y., Malik, S.A., Andryushkova, A., Schroeder, S., Pendl, T., Harger, A., Niso-Santano, M., Zamzami, N., Scoazec, M., Durand, S., Enot, D.P., Fernandez, A.F., Martins, I., Kepp, O., Senovilla, L., Bauvy, C., Morselli, E., Vacchelli, E., Bennetzen, M., Magnes, C., Sinner, F., Pieber, T., Lopez-Otin, C., Maiuri, M.C., Codogno, P., Andersen, J.S., Hill, J.A., Madeo, F. and Kroemer, G. (2014) Regulation of autophagy by cytosolic acetyl-coenzyme A. Mol. Cell 53, 710-725
149. Mason, M.G., Nicholls, P., Wilson, M.T. and Cooper, C.E. (2006) Nitric oxide inhibition of respiration involves both competitive (heme) and noncompetitive (copper) binding to cytochrome c oxidase. Proc. Natl. Acad. Sci. U.S.A. 103, 708-713
150. McLain, A.L., Szweda, P.A. and Szweda, L.I. (2011) Alpha-Ketoglutarate dehydrogenase: a mitochondrial redox sensor. Free Radic. Res. 45, 29-36
151. Metallo, C.M. and Vander Heiden, M.G. (2010) Metabolism strikes back: metabolic flux regulates cell signaling. Genes Dev. 24, 2717-2722
152. Michal, G. and Schomburg, D. (2013). Biochemical pathways: an atlas of biochemistry and molecular biology, John Wiley & Sons, New York.
153. Migita, T., Narita, T., Nomura, K., Miyagi, E., Inazuka, F., Matsuura, M., Ushijima, M., Mashima, T., Seimiya, H., Satoh, Y., Okumura, S., Nakagawa, K. and Ishikawa, Y. (2008) ATP citrate lyase: activation and therapeutic implications in non-small cell lung cancer. Cancer Res. 68, 8547-8554
154. Mihaylova, M.M. and Shaw, R.J. (2011) The AMPK signalling pathway coordinates cell growth, autophagy and metabolism. Nat. Cell Biol. 13, 1016-1023
155. Molina y, Vedia, L., McDonald, B., Reep, B., Brune, B., Di Silvio, M., Billiar, T.R. and Lapetina, E.G. (1992) Nitric oxide-induced S-nitrosylation of glyceraldehyde-3-phosphate dehydrogenase inhibits enzymatic activity and increases endogenous ADP-ribosylation. J. Biol. Chem. 267, 24929-24932
156. Moss, J., Watkins, P.A., Stanley, S.J., Purnell, M.R. and Kidwell, W.R. (1984) Inactivation of glutamine synthetases by an NAD:arginine ADP-ribosyltransferase. J. Biol. Chem. 259, 5100-5104
157. Mullen, A.R. and DeBerardinis, R.J. (2012) Genetically-defined metabolic reprogramming in cancer. Trends Endocrinol. Metab. 23, 552-559
158. Mullen, A.R., Hu, Z., Shi, X., Jiang, L., Boroughs, L.K., Kovacs, Z., Boriack, R., Rakheja, D., Sullivan, L.B., Linehan, W.M., Chandel, N.S. and DeBerardinis, R.J. (2014) Oxidation of alpha-ketoglutarate is required for reductive carboxylation in cancer cells with mitochondrial defects. Cell Rep. 7, 1679-1690
159. Nakagawa, T., Lomb, D.J., Haigis, M.C. and Guarente, L. (2009) SIRT5 Deacetylates carbamoyl phosphate synthetase 1 and regulates the urea cycle. Cell 137, 560-570
160. Newman, J.C., He, W. and Verdin, E. (2012) Mitochondrial protein acylation and intermediary metabolism: regulation by sirtuins and implications for metabolic disease. J. Biol. Chem. 287, 42436-42443
161. Newman, R.H., Zhang, J. and Zhu, H. (2014) Toward a systems-level view of dynamic phosphorylation networks. Front. Genet. 5, 263
162. Nguyen, A.T. and Donaldson, R.P. (2005) Metal-catalyzed oxidation induces carbonylation of peroxisomal proteins and loss of enzymatic activities. Arch. Biochem. Biophys. 439, 25-31
163. Nicklin, P., Bergman, P., Zhang, B., Triantafellow, E., Wang, H., Nyfeler, B., Yang, H., Hild, M., Kung, C., Wilson, C., Myer, V.E., MacKeigan, J.P., Porter, J.A., Wang, Y.K., Cantley, L.C., Finan, P.M. and Murphy, L.O. (2009) Bidirectional transport of amino acids regulates mTOR and autophagy. Cell 136, 521-534
164. Niitsu, Y., Hori, O., Yamaguchi, A., Bando, Y., Ozawa, K., Tamatani, M., Ogawa, S. and Tohyama, M. (1999) Exposure of cultured primary rat astrocytes to hypoxia results in intracellular glucose depletion and induction of glycolytic enzymes. Brain Res. Mol. Brain Res. 74, 26-34
165. Nordlie, R.C., Foster, J.D. and Lange, A.J. (1999) Regulation of glucose production by the liver. Annu. Rev. Nutr. 19, 379-406
166. Nulton-Persson, A.C., Starke, D.W., Mieyal, J.J. and Szweda, L.I. (2003) Reversible inactivation of alpha-ketoglutarate dehydrogenase in response to alterations in the mitochondrial glutathione status. Biochemistry 42, 4235-4242
167. O'Neill, H.M., Lally, J.S., Galic, S., Thomas, M., Azizi, P.D., Fullerton, M.D., Smith, B.K., Pulinilkunnil, T., Chen, Z., Samaan, M.C., Jorgensen, S.B., Dyck, J.R., Holloway, G.P., Hawke, T.J., vanDenderen, B.J., Kemp, B.E. and Steinberg, G.R. (2014) AMPK phosphorylation of ACC2 is required for skeletal muscle fatty acid oxidation and insulin sensitivity in mice. Diabetologia 57, 1693-1702
168. Oh, W.J. and Jacinto, E. (2011) mTOR complex 2 signaling and functions. Cell Cycle 10, 2305-2316
169. Okorokov, A.L. and Milner, J. (1999) An ATP/ADP-dependent molecular switch regulates the stability of p53-DNA complexes. Mol. Cell Biol. 19, 7501-7510
170. Okoshi, R., Ozaki, T., Yamamoto, H., Ando, K., Koida, N., Ono, S., Koda, T., Kamijo, T., Nakagawara, A. and Kizaki, H. (2008) Activation of AMP-activated protein kinase induces p53-dependent apoptotic cell death in response to energetic stress. J. Biol. Chem. 283, 3979-3987
171. Onishi, Y., Hirasaka, K., Ishihara, I., Oarada, M., Goto, J., Ogawa, T., Suzue, N., Nakano, S., Furochi, H., Ishidoh, K., Kishi, K. and Nikawa, T. (2005) Identification of mono-ubiquitinated LDH-A in skeletal muscle cells exposed to oxidative stress. Biochem. Biophys. Res. Commun. 336, 799-806
172. Ota, S., Horigome, K., Ishii, T., Nakai, M., Hayashi, K., Kawamura, T., Kishino, A., Taiji, M. and Kimura, T. (2009) Metformin suppresses glucose-6-phosphatase expression by a complex I inhibition and AMPK activation-independent mechanism. Biochem. Biophys. Res. Commun. 388, 311-316
173. Ozden, O., Park, S.H., Wagner, B.A., Yong Song, H., Zhu, Y., Vassilopoulos, A., Jung, B., Buettner, G.R. and Gius, D. (2014) SIRT3 deacetylates and increases pyruvate dehydrogenase activity in cancer cells. Free Radic. Biol. Med. 76, 163-172
174. Padrao, A.I., Ferreira, R.M., Vitorino, R., Alves, R.M., Neuparth, M.J., Duarte, J.A. and Amado, F. (2011) OXPHOS susceptibility to oxidative modifications: the role of heart mitochondrial subcellular location. Biochim. Biophys. Acta 1807, 1106-1113
175. Paneni, F., Costantino, S. and Cosentino, F. (2014) Insulin resistance, diabetes, and cardiovascular risk. Curr. Atheroscler. Rep. 16, 419
176. Park, J., Chen, Y., Tishkoff, D.X., Peng, C., Tan, M., Dai, L., Xie, Z., Zhang, Y., Zwaans, B.M., Skinner, M.E., Lombard, D.B. and Zhao, Y. (2013) SIRT5-mediated lysine desuccinylation impacts diverse metabolic pathways. Mol. Cell 50, 919-930
177. Park, S.H., Gammon, S.R., Knippers, J.D., Paulsen, S.R., Rubink, D.S. and Winder, W.W. (2002) Phosphorylation-activity relationships of AMPK and acetyl-CoA carboxylase in muscle. J. Appl. Physiol. (1985) 92, 2475-2482
178. Peng, C., Lu, Z., Xie, Z., Cheng, Z., Chen, Y., Tan, M., Luo, H., Zhang, Y., He, W., Yang, K., Zwaans, B.M., Tishkoff, D., Ho, L., Lombard, D., He, T.C., Dai, J., Verdin, E., Ye, Y. and Zhao, Y. (2011) The first identification of lysine malonylation substrates and its regulatory enzyme. Mol. Cell. Proteomics 10, M111 012658
179. Pierce, M.W., Palmer, J.L., Keutmann, H.T. and Avruch, J. (1981) ATP-citrate lyase. Structure of a tryptic peptide containing the phosphorylation site directed by glucagon and the cAMP-dependent protein kinase. J. Biol. Chem. 256, 8867-8870
180. Polak, P. and Hall, M.N. (2009) mTOR and the control of whole body metabolism. Curr. Opin. Cell Biol. 21, 209-218
181. Poorman, R.A., Randolph, A., Kemp, R.G. and Heinrikson, R.L. (1984) Evolution of phosphofructokinase-gene duplication and creation of new effector sites. Nature 309, 467-469
182. Porstmann, T., Santos, C.R., Griffiths, B., Cully, M., Wu, M., Leevers, S., Griffiths, J.R., Chung, Y.L. and Schulze, A. (2008) SREBP activity is regulated by mTORC1 and contributes to Akt-dependent cell growth. Cell Metab. 8, 224-236
183. Potapova, I.A., El-Maghrabi, M.R., Doronin, S.V. and Benjamin, W.B. (2000) Phosphorylation of recombinant human ATP:citrate lyase by cAMP-dependent protein kinase abolishes homotropic allosteric regulation of the enzyme by citrate and increases the enzyme activity. Allosteric activation of ATP:citrate lyase by phosphorylated sugars. Biochemistry 39, 1169-1179
184. Puzio-Kuter, A.M. (2011) The Role of p53 in Metabolic Regulation. Genes Cancer 2, 385-391
185. Qi, L., Heredia, J.E., Altarejos, J.Y., Screaton, R., Goebel, N., Niessen, S., Macleod, I.X., Liew, C.W., Kulkarni, R.N., Bain, J., Newgard, C., Nelson, M., Evans, R.M., Yates, J. and Montminy, M. (2006) TRB3 links the E3 ubiquitin ligase COP1 to lipid metabolism. Science 312, 1763-1766
186. Ramsdell, J.S. and Gulland, F.M. (2014) Domoic acid epileptic disease. Mar. Drugs 12, 1185-1207
187. Rebsamen, M., Pochini, L., Stasyk, T., deAraujo, M.E., Galluccio, M., Kandasamy, R.K., Snijder, B., Fauster, A., Rudashevskaya, E.L., Bruckner, M., Scorzoni, S., Filipek, P.A., Huber, K.V., Bigenzahn, J.W., Heinz, L.X., Kraft, C., Bennett, K.L., Indiveri, C., Huber, L.A. and Superti-Furga, G. (2015) SLC38A9 is a component of the lysosomal amino acid sensing machinery that controls mTORC1. Nature 519(7544), 477-481
188. Reczek, C.R. and Chandel, N.S. (2015) ROS-dependent signal transduction. Curr. Opin. Cell Biol. 33, 8-13
189. Reed, T.T., Pierce, W.M., Markesbery, W.R. and Butterfield, D.A. (2009) Proteomic identification of HNE-bound proteins in early Alzheimer disease: Insights into the role of lipid peroxidation in the progression of AD. Brain Res. 1274, 66-76
190. Regard, J.B., Sato, I.T. and Coughlin, S.R. (2008) Anatomical profiling of G protein-coupled receptor expression. Cell 135, 561-571
191. Reitzer, L.J., Wice, B.M. and Kennell, D. (1979) Evidence that glutamine, not sugar, is the major energy source for cultured HeLa cells. J. Biol. Chem. 254, 2669-2676
192. Roberts, D.J. and Miyamoto, S. (2015) Hexokinase II integrates energy metabolism and cellular protection: Akting on mitochondria and TORCing to autophagy. Cell Death Differ 22(2), 248-257
193. Roberts, D.J., Tan-Sah, V.P., Ding, E.Y., Smith, J.M. and Miyamoto, S. (2014) Hexokinase-II positively regulates glucose starvation-induced autophagy through TORC1 inhibition. Mol. Cell 53, 521-533
194. Roberts, D.L., Dive, C. and Renehan, A.G. (2010) Biological mechanisms linking obesity and cancer risk: new perspectives. Annu. Rev. Med. 61, 301-316
195. Robitaille, A.M., Christen, S., Shimobayashi, M., Cornu, M., Fava, L.L., Moes, S., Prescianotto-Baschong, C., Sauer, U., Jenoe, P. and Hall, M.N. (2013) Quantitative phosphoproteomics reveal mTORC1 activates de novo pyrimidine synthesis. Science 339, 1320-1323
196. Rosa, J.L., Perez, J.X., Ventura, F., Tauler, A., Gil, J., Shimoyama, M., Pilkis, S.J. and Bartrons, R. (1995) Role of the N-terminal region in covalent modification of 6-phosphofructo-2-kinase/fructose-2, 6-bisphosphatase: comparison of phosphorylation and ADP-ribosylation. Biochem. J. 309, 119-125
197. Ruan, H.B., Nie, Y. and Yang, X. (2013) Regulation of protein degradation by O-GlcNAcylation: crosstalk with ubiquitination. Mol. Cell. Proteomics 12, 3489-3497
198. Ryan, B.J., Nissim, A. and Winyard, P.G. (2014) Oxidative post-translational modifications and their involvement in the pathogenesis of autoimmune diseases. Redox. Biol. 2, 715-724
199. Ryan, K., Backos, D.S., Reigan, P. and Patel, M. (2012) Post-translational oxidative modification and inactivation of mitochondrial complex I in epileptogenesis. J. Neurosci. 32, 11250-11258
200. Sabharwal, S.S. and Schumacker, P.T. (2014) Mitochondrial ROS in cancer: initiators, amplifiers or an Achilles' heel? Nat. Rev. Cancer 14, 709-721
201. Sancak, Y. and Sabatini, D.M. (2009) Rag proteins regulate amino-acid-induced mTORC1 signalling. Biochem Soc. Trans. 37, 289-290
202. Sanchez-Cenizo, L., Formentini, L., Aldea, M., Ortega, A.D., Garcia-Huerta, P., Sanchez-Arago, M. and Cuezva, J.M. (2010) Up-regulation of the ATPase inhibitory factor 1 (IF1) of the mitochondrial H+-ATP synthase in human tumors mediates the metabolic shift of cancer cells to a Warburg phenotype. J. Biol. Chem. 285, 25308-25313
203. Sauve, A.A. and Youn, D.Y. (2012) Sirtuins: NAD(+)-dependent deacetylase mechanism and regulation. Curr. Opin. Chem. Biol. 16, 535-543
204. Schapira, A.H. (2008) Mitochondrial dysfunction in neurodegenerative diseases. Neurochem. Res. 33, 2502-2509
205. Schlicker, C., Gertz, M., Papatheodorou, P., Kachholz, B., Becker, C.F. and Steegborn, C. (2008) Substrates and regulation mechanisms for the human mitochondrial sirtuins Sirt3 and Sirt5. J. Mol. Biol. 382, 790-801
206. Schweizer, M. and Richter, C. (1994) Nitric oxide potently and reversibly deenergizes mitochondria at low oxygen tension. Biochem. Biophys. Res. Commun. 204, 169-175
207. Schwer, B., Bunkenborg, J., Verdin, R.O., Andersen, J.S. and Verdin, E. (2006) Reversible lysine acetylation controls the activity of the mitochondrial enzyme acetyl-CoA synthetase 2. Proc. Natl. Acad. Sci. U.S.A. 103, 10224-10229
208. Semenza, G.L. (2010) HIF-1: upstream and downstream of cancer metabolism. Curr. Opin. Genet. Dev. 20, 51-56
209. Seo, M. and Lee, Y.H. (2014) PFKFB3 regulates oxidative stress homeostasis via its S-glutathionylation in cancer. J. Mol. Biol. 426, 830-842
210. Shan, C., Elf, S., Ji, Q., Kang, H.B., Zhou, L., Hitosugi, T., Jin, L., Lin, R., Zhang, L., Seo, J.H., Xie, J., Tucker, M., Gu, T.L., Sudderth, J., Jiang, L., DeBerardinis, R.J., Wu, S., Li, Y., Mao, H., Chen, P.R., Wang, D., Chen, G.Z., Lonial, S., Arellano, M.L., Khoury, H.J., Khuri, F.R., Lee, B.H., Brat, D.J., Ye, K., Boggon, T.J., He, C., Kang, S., Fan, J. and Chen, J. (2014) Lysine acetylation activates 6-phosphogluconate dehydrogenase to promote tumor growth. Mol. Cell 55, 552-565
211. Shanware, N.P., Bray, K., Eng, C.H., Wang, F., Follettie, M., Myers, J., Fantin, V.R. and Abraham, R.T. (2014) Glutamine deprivation stimulates mTOR-JNK-dependent chemokine secretion. Nat. Commun. 5, 4900
212. She, P., Reid, T.M., Bronson, S.K., Vary, T.C., Hajnal, A., Lynch, C.J. and Hutson, S.M. (2007) Disruption of BCATm in mice leads to increased energy expenditure associated with the activation of a futile protein turnover cycle. Cell Metab. 6, 181-194
213. Shinohara, Y., Yamamoto, K., Kogure, K., Ichihara, J. and Terada, H. (1994) Steady state transcript levels of the type II hexokinase and type 1 glucose transporter in human tumor cell lines. Cancer Lett. 82, 27-32
214. Shirwany, N.A. and Zou, M.H. (2014) AMPK: a cellular metabolic and redox sensor. A minireview. Front. Biosci. (Landmark Ed) 19, 447-474
215. Sledz, P., Forster, F. and Baumeister, W. (2013) Allosteric effects in the regulation of 26S proteasome activities. J. Mol. Biol. 425, 1415-1423
216. Son, H.J., Ha, S.C., Hwang, E.Y., Kim, E.A., Ahn, J.Y., Choi, S.Y. and Cho, S.W. (2012) Roles of cysteine residues in the inhibition of human glutamate dehydrogenase by palmitoyl-CoA. BMB Rep. 45, 707-712.
217. Sundstrom, L., Greasley, P.J., Engberg, S., Wallander, M. and Ryberg, E. (2013) Succinate receptor GPR91, a Galpha(i) coupled receptor that increases intracellular calcium concentrations through PLCbeta. FEBS Lett. 587, 2399-2404
218. Ternette, N., Yang, M., Laroyia, M., Kitagawa, M., O'Flaherty, L., Wolhulter, K., Igarashi, K., Saito, K., Kato, K., Fischer, R., Berquand, A., Kessler, B.M., Lappin, T., Frizzell, N., Soga, T., Adam, J. and Pollard, P.J. (2013) Inhibition of mitochondrial aconitase by succination in fumarate hydratase deficiency. Cell Rep. 3, 689-700
219. Tisdale, E.J. (2002) Glyceraldehyde-3-phosphate dehydrogenase is phosphorylated by protein kinase Ciota /lambda and plays a role in microtubule dynamics in the early secretory pathway. J. Biol. Chem. 277, 3334-3341
220. Tomita, T., Kuzuyama, T. and Nishiyama, M. (2011) Structural basis for leucine-induced allosteric activation of glutamate dehydrogenase. J. Biol. Chem. 286, 37406-37413
221. Tong, W.H., Sourbier, C., Kovtunovych, G., Jeong, S.Y., Vira, M., Ghosh, M., Romero, V.V., Sougrat, R., Vaulont, S., Viollet, B., Kim, Y.S., Lee, S., Trepel, J., Srinivasan, R., Bratslavsky, G., Yang, Y., Linehan, W.M. and Rouault, T.A. (2011) The glycolytic shift in fumarate-hydratase-deficient kidney cancer lowers AMPK levels, increases anabolic propensities and lowers cellular iron levels. Cancer Cell 20, 315-327
222. Tripathy, S. and Jump, D.B. (2013) Elovl5 regulates the mTORC2-Akt-FOXO1 pathway by controlling hepatic cis-vaccenic acid synthesis in diet-induced obese mice. J. Lipid Res. 54, 71-84
223. Tsusaka, T., Guo, T., Yagura, T., Inoue, T., Yokode, M., Inagaki, N. and Kondoh, H. (2014) Deacetylation of phosphoglycerate mutase in its distinct central region by SIRT2 down-regulates its enzymatic activity. Genes Cells 19, 766-777
224. Vander Heiden, M.G., Cantley, L.C. and Thompson, C.B. (2009) Understanding the Warburg effect: the metabolic requirements of cell proliferation. Science 324, 1029-1033
225. Vander Heiden, M.G., Locasale, J.W., Swanson, K.D., Sharfi, H., Heffron, G.J., Amador-Noguez, D., Christofk, H.R., Wagner, G., Rabinowitz, J.D., Asara, J.M. and Cantley, L.C. (2010) Evidence for an alternative glycolytic pathway in rapidly proliferating cells. Science 329, 1492-1499
226. Vaziri, H., Dessain, S.K., Ng Eaton, E., Imai, S.I., Frye, R.A., Pandita, T.K., Guarente, L. and Weinberg, R.A. (2001) hSIR2(SIRT1) functions as an NAD-dependent p53 deacetylase. Cell 107, 149-159
227. Ventura, M., Mateo, F., Serratosa, J., Salaet, I., Carujo, S., Bachs, O. and Pujol, M.J. (2010) Nuclear translocation of glyceraldehyde-3-phosphate dehydrogenase is regulated by acetylation. Int. J. Biochem. Cell Biol. 42, 1672-1680
228. Vivanco, I. (2014) Targeting molecular addictions in cancer. Br. J. Cancer 111, 2033-2038
229. Vousden, K.H. and Ryan, K.M. (2009) p53 and metabolism. Nat. Rev. Cancer 9, 691-700
230. Wagner, G.R. and Payne, R.M. (2013) Widespread and enzyme-independent Nepsilon-acetylation and Nepsilon-succinylation of proteins in the chemical conditions of the mitochondrial matrix. J. Biol. Chem. 288, 29036-29045
231. Wagner, P.D. and Vu, N.D. (1995) Phosphorylation of ATP-citrate lyase by nucleoside diphosphate kinase. J. Biol. Chem. 270, 21758-21764
232. Wagner, S.A., Beli, P., Weinert, B.T., Nielsen, M.L., Cox, J., Mann, M. and Choudhary, C. (2011) A proteome-wide, quantitative survey of in vivo ubiquitylation sites reveals widespread regulatory roles. Mol. Cell. Proteomics 10, M111 013284
233. Walsh, C.T., Garneau-Tsodikova, S. and G.J. Gatto, Jr. (2005) Protein posttranslational modifications: the chemistry of proteome diversifications. Angew. Chem. Int. Ed. Engl. 44, 7342-7372
234. Wang, S., Tsun, Z.Y., Wolfson, R.L., Shen, K., Wyant, G.A., Plovanich, M.E., Yuan, E.D., Jones, T.D., Chantranupong, L., Comb, W., Wang, T., Bar-Peled, L., Zoncu, R., Straub, C., Kim, C., Park, J., Sabatini, B.L. and Sabatini, D.M. (2015) Metabolism. Lysosomal amino acid transporter SLC38A9 signals arginine sufficiency to mTORC1. Science 347(6218), 188-194
235. Wang, S.B., Foster, D.B., Rucker, J., O'Rourke, B., Kass, D.A. and VanEyk, J.E. (2011) Redox regulation of mitochondrial ATP synthase: implications for cardiac resynchronization therapy. Circ. Res. 109, 750-757
236. Wang, W. and Guan, K.L. (2009) AMP-activated protein kinase and cancer. Acta Physiol. (Oxf.) 196, 55-63
237. Wang, X., Campbell, L.E., Miller, C.M. and Proud, C.G. (1998) Amino acid availability regulates p70 S6 kinase and multiple translation factors. Biochem. J. 334, 261-267
238. Wang, Y.P., Zhou, L.S., Zhao, Y.Z., Wang, S.W., Chen, L.L., Liu, L.X., Ling, Z.Q., Hu, F.J., Sun, Y.P., Zhang, J.Y., Yang, C., Yang, Y., Xiong, Y., Guan, K.L. and Ye, D. (2014) Regulation of G6PD acetylation by SIRT2 and KAT9 modulates NADPH homeostasis and cell survival during oxidative stress. EMBO J. 33, 1304-1320
239. Wellen, K.E., Hatzivassiliou, G., Sachdeva, U.M., Bui, T.V., Cross, J.R. and Thompson, C.B. (2009) ATP-citrate lyase links cellular metabolism to histone acetylation. Science 324, 1076-1080
240. Wellen, K.E., Lu, C., Mancuso, A., Lemons, J.M., Ryczko, M., Dennis, J.W., Rabinowitz, J.D., Coller, H.A. and Thompson, C.B. (2010) The hexosamine biosynthetic pathway couples growth factor-induced glutamine uptake to glucose metabolism. Genes Dev. 24, 2784-2799
241. Wice, B.M., Reitzer, L.J. and Kennell, D. (1981) The continuous growth of vertebrate cells in the absence of sugar. J. Biol. Chem. 256, 7812-7819
242. Wolf, A., Agnihotri, S., Micallef, J., Mukherjee, J., Sabha, N., Cairns, R., Hawkins, C. and Guha, A. (2011) Hexokinase 2 is a key mediator of aerobic glycolysis and promotes tumor growth in human glioblastoma multiforme. J. Exp. Med. 208, 313-326
243. Xu, W., Li, Y., Liu, C. and Zhao, S. (2014a) Protein lysine acetylation guards metabolic homeostasis to fight against cancer. Oncogene 33, 2279-2285
244. Xu, Y., Li, F., Lv, L., Li, T., Zhou, X., Deng, C.X., Guan, K.L., Lei, Q.Y. and Xiong, Y. (2014b) Oxidative stress activates SIRT2 to deacetylate and stimulate phosphoglycerate mutase. Cancer Res. 74, 3630-3642
245. Xu, Y., Osborne, B.W. and Stanton, R.C. (2005) Diabetes causes inhibition of glucose-6-phosphate dehydrogenase via activation of PKA, which contributes to oxidative stress in rat kidney cortex. Am. J. Physiol. Renal. Physiol. 289, F1040-F1047
246. Yan, L.J., Levine, R.L. and Sohal, R.S. (1997) Oxidative damage during aging targets mitochondrial aconitase. Proc. Natl. Acad. Sci. U.S.A. 94, 11168-11172
247. Yang, M., Ternette, N., Su, H., Dabiri, R., Kessler, B.M., Adam, J., Teh, B.T. and Pollard, P.J. (2014) The succinated proteome of FH-mutant tumours. Metabolites 4, 640-654
248. Yang, W., Zheng, Y., Xia, Y., Ji, H., Chen, X., Guo, F., Lyssiotis, C.A., Aldape, K., Cantley, L.C. and Lu, Z. (2012) ERK1/2-dependent phosphorylation and nuclear translocation of PKM2 promotes the Warburg effect. Nat. Cell Biol. 14, 1295-1304
249. Ye, J., Fan, J., Venneti, S., Wan, Y.W., Pawel, B.R., Zhang, J., Finley, L.W., Lu, C., Lindsten, T., Cross, J.R., Qing, G., Liu, Z., Simon, M.C., Rabinowitz, J.D. and Thompson, C.B. (2014) Serine catabolism regulates mitochondrial redox control during hypoxia. Cancer Discov. 4, 1406-1417
250. Ye, J., Mancuso, A., Tong, X., Ward, P.S., Fan, J., Rabinowitz, J.D. and Thompson, C.B. (2012) Pyruvate kinase M2 promotes de novo serine synthesis to sustain mTORC1 activity and cell proliferation. Proc. Natl. Acad. Sci. U.S.A. 109, 6904-6909
251. Yi, J. and Luo, J. (2010) SIRT1 and p53, effect on cancer, senescence and beyond. Biochim. Biophys. Acta 1804, 1684-1689
252. Yi, W., Clark, P.M., Mason, D.E., Keenan, M.C., Hill, C., Goddard, W.A., 3rd, Peters, E.C., Driggers, E.M. and Hsieh-Wilson, L.C. (2012) Phosphofructokinase 1 glycosylation regulates cell growth and metabolism. Science 337, 975-980
253. Yokoyama, C., Wang, X., Briggs, M.R., Admon, A., Wu, J., Hua, X., Goldstein, J.L. and Brown, M.S. (1993) SREBP-1, a basic-helix-loop-helix-leucine zipper protein that controls transcription of the low density lipoprotein receptor gene. Cell 75, 187-197
254. Yonezawa, K., Tokunaga, C., Oshiro, N. and Yoshino, K. (2004) Raptor, a binding partner of target of rapamycin. Biochem. Biophys. Res. Commun. 313, 437-441
255. Yu, W., Dittenhafer-Reed, K.E. and Denu, J.M. (2012) SIRT3 protein deacetylates isocitrate dehydrogenase 2 (IDH2) and regulates mitochondrial redox status. J. Biol. Chem. 287, 14078-14086
256. Zhang, F., Paterson, A.J., Huang, P., Wang, K. and Kudlow, J.E. (2007) Metabolic control of proteasome function. Physiology (Bethesda) 22, 373-379
257. Zhang, F., Su, K., Yang, X., Bowe, D.B., Paterson, A.J. and Kudlow, J.E. (2003) O-GlcNAc modification is an endogenous inhibitor of the proteasome. Cell 115, 715-725
258. Zhang, J., Jin, B., Li, L., Block, E.R. and Patel, J.M. (2005) Nitric oxide-induced persistent inhibition and nitrosylation of active site cysteine residues of mitochondrial cytochrome-c oxidase in lung endothelial cells. Am. J. Physiol. Cell Physiol. 288, C840-C849
259. Zhang, J. and Snyder, S.H. (1992) Nitric oxide stimulates auto-ADP-ribosylation of glyceraldehyde-3-phosphate dehydrogenase. Proc. Natl. Acad. Sci. U.S.A. 89, 9382-9385
260. Zhang, Z., Apse, K., Pang, J. and Stanton, R.C. (2000) High glucose inhibits glucose-6-phosphate dehydrogenase via cAMP in aortic endothelial cells. J. Biol. Chem. 275, 40042-40047
261. Zhang, Z., Tan, M., Xie, Z., Dai, L., Chen, Y. and Zhao, Y. (2011) Identification of lysine succinylation as a new post-translational modification. Nat. Chem. Biol. 7, 58-63
262. Zhao, S., Xu, W., Jiang, W., Yu, W., Lin, Y., Zhang, T., Yao, J., Zhou, L., Zeng, Y., Li, H., Li, Y., Shi, J., An, W., Hancock, S.M., He, F., Qin, L., Chin, J., Yang, P., Chen, X., Lei, Q., Xiong, Y. and Guan, K.L. (2010) Regulation of cellular metabolism by protein lysine acetylation. Science 327, 1000-1004
263. Zoncu, R., Bar-Peled, L., Efeyan, A., Wang, S., Sancak, Y. and Sabatini, D.M. (2011) mTORC1 senses lysosomal amino acids through an inside-out mechanism that requires the vacuolar H(+)-ATPase. Science 334, 678-683