Mitochondrial Sirtuins and Their Relationships with Metabolic Disease and Cancer

Antioxidants and Redox Signaling

Volumn 22, Issue 12, 2015, Pages 1060-1077

  Kumar, Surinder ^a   Lombard, David B ^a,b  

^a UNIVERSITY OF MICHIGAN MEDICAL SCHOOL   (United States)

^b UNIVERSITY OF MICHIGAN HEALTH SYSTEM   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

MITOCHONDRIAL PROTEIN; ORNITHINE CARBAMOYLTRANSFERASE; PYRUVATE DEHYDROGENASE COMPLEX; SIRTUIN; SIRTUIN 2; SIRTUIN 3; SIRTUIN 4; SIRTUIN 5; SIRTUIN 6; SIRTUIN 7; GLUTAMINE;

ACYLATION; APOPTOSIS; CANCER CELL; CARCINOGENESIS; CELL PROLIFERATION; CELL SURVIVAL; CELLULAR DISTRIBUTION; CIRCADIAN RHYTHM; FATTY ACID METABOLISM; FATTY ACID OXIDATION; GLUCOSE OXIDATION; HEART VENTRICLE HYPERTROPHY; HEMATOPOIETIC STEM CELL; HOMEOSTASIS; HUMAN; INSULIN SENSITIVITY; INTRACELLULAR SIGNALING; KETOGENESIS; METABOLIC DISORDER; METABOLIC REGULATION; NEOPLASM; NONHUMAN; OXIDATIVE STRESS; OXYGEN CONSUMPTION; PRIORITY JOURNAL; PROTEIN ACETYLATION; PROTEIN EXPRESSION; PROTEIN FUNCTION; RESPIRATORY CHAIN; REVIEW; TUMOR PROMOTION; UNFOLDED PROTEIN RESPONSE; UREA CYCLE; AGING; ANIMAL; METABOLISM;

AGING; ANIMALS; CARCINOGENESIS; GLUTAMINE; HOMEOSTASIS; HUMANS; METABOLIC DISEASES; MITOCHONDRIAL PROTEINS; NEOPLASMS; SIRTUINS;

EID: 84926628054     PISSN: 15230864     EISSN: 15577716     Source Type: Journal    
DOI: 10.1089/ars.2014.6213     Document Type: Review

References (179)

1. Ahn BH, Kim HS, Song S, Lee IH, Liu J, Vassilopoulos A, Deng CX, and Finkel T. A role for the mitochondrial deacetylase Sirt3 in regulating energy homeostasis. Proc Natl Acad Sci U S A 105: 14447-14452, 2008.
2. Ahuja N, Schwer B, Carobbio S, Waltregny D, North BJ, Castronovo V, Maechler P, and Verdin E. Regulation of insulin secretion by SIRT4, a mitochondrial ADP-ribosyltransferase. J Biol Chem 282: 33583-33592, 2007.
3. Alam N and Saggerson ED. Malonyl-CoA and the regulation of fatty acid oxidation in soleus muscle. Biochem J 334 (Pt 1): 233-241, 1998.
4. Albani D, Ateri E, Mazzuco S, Ghilardi A, Rodilossi S, Biella G, Ongaro F, Antuono P, Boldrini P, Di Giorgi E, Frigato A, Durante E, Caberlotto L, Zanardo A, Siculi M, Gallucci M, and Forloni G. Modulation of human longevity by SIRT3 single nucleotide polymorphisms in the prospective study "Treviso Longeva (TRELONG)". Age (Dordr) 36: 469-478, 2014.
5. Alhazzazi TY, Kamarajan P, Joo N, Huang JY, Verdin E, D'Silva NJ, and Kapila YL. Sirtuin-3 (SIRT3), a novel potential therapeutic target for oral cancer. Cancer 117: 1670-1678, 2011.
6. Alvarez-Lario B and Macarron-Vicente J. Uric acid and evolution. Rheumatology (Oxford) 49: 2010-2015, 2010.
7. Ashraf N, Zino S, Macintyre A, Kingsmore D, Payne AP, George WD, and Shiels PG. Altered sirtuin expression is associated with node-positive breast cancer. Br J Cancer 95: 1056-1061, 2006.
8. Aury-Landas J, Bougeard G, Castel H, Hernandez-Vargas H, Drouet A, Latouche JB, Schouft MT, Ferec C, Leroux D, Lasset C, Coupier I, Caron O, Herceg Z, Frebourg T, and Flaman JM. Germline copy number variation of genes involved in chromatin remodelling in families suggestive of Li-Fraumeni syndrome with brain tumours. Eur J Hum Genet 21: 1369-1376, 2013.
9. Bao J, Scott I, Lu Z, Pang L, Dimond CC, Gius D, and Sack MN. SIRT3 is regulated by nutrient excess and modulates hepatic susceptibility to lipotoxicity. Free Radic Biol Med 49: 1230-1237, 2010.
10. Bao X, Wang Y, Li X, Li XM, Liu Z, Yang T, Wong CF, Zhang J, Hao Q, and Li XD. Identification of 'erasers' for lysine crotonylated histone marks using a chemical proteomics approach. Elife 3, 2014; DOI: 10.7554/eLife.02999.
11. Bell EL, Emerling BM, Ricoult SJ, and Guarente L. SirT3 suppresses hypoxia inducible factor 1alpha and tumor growth by inhibiting mitochondrial ROS production. Oncogene 30: 2986-2996, 2011.
12. Bellizzi D, Rose G, Cavalcante P, Covello G, Dato S, De Rango F, Greco V, Maggiolini M, Feraco E, Mari V, Franceschi C, Passarino G, and De Benedictis G. A novel VNTR enhancer within the SIRT3 gene, a human homologue of SIR2, is associated with survival at oldest ages. Genomics 85: 258-263, 2005.
13. Blaveri E, Simko JP, Korkola JE, Brewer JL, Baehner F, Mehta K, Devries S, Koppie T, Pejavar S, Carroll P, and Waldman FM. Bladder cancer outcome and subtype classification by gene expression. Clin Cancer Res 11: 4044-4055, 2005.
14. Brenmoehl J and Hoeflich A. Dual control of mitochondrial biogenesis by sirtuin 1 and sirtuin 3. Mitochondrion 13: 755-761, 2013.
15. Brown K, Xie S, Qiu X, Mohrin M, Shin J, Liu Y, Zhang D, Scadden DT, and Chen D. SIRT3 reverses aging-associated degeneration. Cell Rep 3: 319-327, 2013.
16. Buler M, Aatsinki SM, Izzi V, Uusimaa J, and Hakkola J. SIRT5 is under the control of PGC-1alpha and AMPK and is involved in regulation of mitochondrial energy metabolism. FASEB J 28: 3225-3237, 2014.
17. Campbell CT, Kolesar JE, and Kaufman BA. Mitochondrial transcription factor A regulates mitochondrial transcription initiation, DNA packaging, and genome copy number. Biochim Biophys Acta 1819: 921-929, 2012.
18. Cancer Genome Atlas Research N. Integrated genomic analyses of ovarian carcinoma. Nature 474: 609-615, 2011.
19. Canto C, Gerhart-Hines Z, Feige JN, Lagouge M, Noriega L, Milne JC, Elliott PJ, Puigserver P, and Auwerx J. AMPK regulates energy expenditure by modulating NAD(+) metabolism and SIRT1 activity. Nature 458: 1056-1060, 2009.
20. Canto C, Jiang LQ, Deshmukh AS, Mataki C, Coste A, Lagouge M, Zierath JR, and Auwerx J. Interdependence of AMPK and SIRT1 for metabolic adaptation to fasting and exercise in skeletal muscle. Cell Metab 11: 213-219, 2010.
21. Chan DC. Mitochondrial fusion and fission in mammals. Annu Rev Cell Dev Biol 22: 79-99, 2006.
22. Chen IC, Chiang WF, Liu SY, Chen PF, and Chiang HC. Role of SIRT3 in the regulation of redox balance during oral carcinogenesis. Mol Cancer 12: 68, 2013.
23. Chen Y, Wang H, Luo G, and Dai X. SIRT4 inhibits cigarette smoke extracts-induced mononuclear cell adhesion to human pulmonary microvascular endothelial cells via regulating NF-kappaB activity. Toxicol Lett 226: 320-327, 2014.
24. Chen Z, Ye X, Tang N, Shen S, Li Z, Niu X, Lu S, and Xu L. The histone acetylranseferase hMOF acetylates Nrf2 and regulates anti-drug responses in human non-small cell lung cancer. Br J Pharmacol 171: 3196-3211, 2014.
25. Choi JE and Mostoslavsky R. Sirtuins, metabolism, and DNA repair. Curr Opin Genet Dev 26C: 24-32, 2014.
26. Choi YL, Tsukasaki K, O'Neill MC, Yamada Y, Onimaru Y, Matsumoto K, Ohashi J, Yamashita Y, Tsutsumi S, Kaneda R, Takada S, Aburatani H, Kamihira S, Nakamura T, Tomonaga M, and Mano H. A genomic analysis of adult T-cell leukemia. Oncogene 26: 1245-1255, 2007.
27. Cimen H, Han MJ, Yang Y, Tong Q, Koc H, and Koc EC. Regulation of succinate dehydrogenase activity by SIRT3 in mammalian mitochondria. Biochemistry 49: 304-311, 2010.
28. Circu ML and Aw TY. Reactive oxygen species, cellular redox systems, and apoptosis. Free Radic Biol Med 48: 749-762, 2010.
29. Colombo SL, Palacios-Callender M, Frakich N, Carcamo S, Kovacs I, Tudzarova S, and Moncada S. 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, 2011.
30. Csibi A, Fendt SM, Li C, Poulogiannis G, Choo AY, Chapski DJ, Jeong SM, Dempsey JM, Parkhitko A, Morrison T, Henske EP, Haigis MC, Cantley LC, Stephanopoulos G, Yu J, and Blenis J. The mTORC1 pathway stimulates glutamine metabolism and cell proliferation by repressing SIRT4. Cell 153: 840-854, 2013.
31. Dai SH, Chen T, Wang YH, Zhu J, Luo P, Rao W, Yang YF, Fei Z, and Jiang XF. Sirt3 protects cortical neurons against oxidative stress via regulating mitochondrial Ca2+ and mitochondrial biogenesis. Int J Mol Sci 15: 14591-14609, 2014.
32. Dominy JE, Jr., Lee Y, Jedrychowski MP, Chim H, Jurczak MJ, Camporez JP, Ruan HB, Feldman J, Pierce K, Mostoslavsky R, Denu JM, Clish CB, Yang X, Shulman GI, Gygi SP, and Puigserver P. The deacetylase Sirt6 activates the acetyltransferase GCN5 and suppresses hepatic gluconeogenesis. Mol Cell 48: 900-913, 2012.
33. Dryden SC, Nahhas FA, Nowak JE, Goustin AS, and Tainsky MA. Role for human SIRT2 NAD-dependent deacetylase activity in control of mitotic exit in the cell cycle. Mol Cell Biol 23: 3173-3185, 2003.
34. Du J, Zhou Y, Su X, Yu JJ, Khan S, Jiang H, Kim J, Woo J, Kim JH, Choi BH, He B, Chen W, Zhang S, Cerione RA, Auwerx J, Hao Q, and Lin H. Sirt5 is a NAD-dependent protein lysine demalonylase and desuccinylase. Science 334: 806-809, 2011.
35. Fan J, Shan C, Kang HB, Elf S, Xie J, Tucker M, Gu TL, Aguiar M, Lonning S, Chen H, Mohammadi M, Britton LM, Garcia BA, Aleckovic M, Kang Y, Kaluz S, Devi N, Van Meir EG, Hitosugi T, Seo JH, Lonial S, Gaddh M, Arellano M, Khoury HJ, Khuri FR, Boggon TJ, Kang S, and Chen J. Tyr phosphorylation of PDP1 toggles recruitment between ACAT1 and SIRT3 to regulate the pyruvate dehydrogenase complex. Mol Cell 53: 534-548, 2014.
36. Feldman JL, Dittenhafer-Reed KE, and Denu JM. Sirtuin catalysis and regulation. J Biol Chem 287: 42419-42427, 2012.
37. Fernandez-Marcos PJ, Jeninga EH, Canto C, Harach T, de Boer VC, Andreux P, Moullan N, Pirinen E, Yamamoto H, Houten SM, Schoonjans K, and Auwerx J. Muscle or liver-specific Sirt3 deficiency induces hyperacetylation of mitochondrial proteins without affecting global metabolic homeostasis. Sci Rep 2: 425, 2012.
38. Finkelstein JE, Hauser ER, Leonard CO, and Brusilow SW. Late-onset ornithine transcarbamylase deficiency in male patients. J Pediatr 117: 897-902, 1990.
39. Finley LW, Carracedo A, Lee J, Souza A, Egia A, Zhang J, Teruya-Feldstein J, Moreira PI, Cardoso SM, Clish CB, Pandolfi PP, and Haigis MC. SIRT3 opposes reprogramming of cancer cell metabolism through HIF1alpha destabilization. Cancer Cell 19: 416-428, 2011.
40. Finley LW, Haas W, Desquiret-Dumas V, Wallace DC, Procaccio V, Gygi SP, and Haigis MC. Succinate dehydrogenase is a direct target of sirtuin 3 deacetylase activity. PLoS One 6: e23295, 2011.
41. Frescas D and Pagano M. Deregulated proteolysis by the F-box proteins SKP2 and beta-TrCP: tipping the scales of cancer. Nat Rev Cancer 8: 438-449, 2008.
42. Frye RA. Phylogenetic classification of prokaryotic and eukaryotic Sir2-like proteins. Biochem Biophys Res Commun 273: 793-798, 2000.
43. Fujino T, Kondo J, Ishikawa M, Morikawa K, and Yamamoto TT. Acetyl-CoA synthetase 2, a mitochondrial matrix enzyme involved in the oxidation of acetate. J Biol Chem 276: 11420-11426, 2001.
44. Gao P, Tchernyshyov I, Chang TC, Lee YS, Kita K, Ochi T, Zeller KI, De Marzo AM, Van Eyk JE, Mendell JT, and Dang CV. c-Myc suppression of miR-23a/b enhances mitochondrial glutaminase expression and glutamine metabolism. Nature 458: 762-765, 2009.
45. Garber ME, Troyanskaya OG, Schluens K, Petersen S, Thaesler Z, Pacyna-Gengelbach M, van de Rijn M, Rosen GD, Perou CM, Whyte RI, Altman RB, Brown PO, Botstein D, and Petersen I. Diversity of gene expression in adenocarcinoma of the lung. Proc Natl Acad Sci U S A 98: 13784-13789, 2001.
46. Geng YQ, Li TT, Liu XY, Li ZH, and Fu YC. SIRT1 and SIRT5 activity expression and behavioral responses to calorie restriction. J Cell Biochem 112: 3755-3761, 2011.
47. Giblin W, Skinner ME, and Lombard DB. Sirtuins: guardians of mammalian healthspan. Trends Genet 30: 271-286, 2014.
48. Gil R, Barth S, Kanfi Y, and Cohen HY. SIRT6 exhibits nucleosome-dependent deacetylase activity. Nucleic Acids Res 41: 8537-8545, 2013.
49. Glasauer A, Sena LA, Diebold LP, Mazar AP, and Chandel NS. Targeting SOD1 reduces experimental non-small-cell lung cancer. J Clin Invest 124: 117-128, 2014.
50. Hafner AV, Dai J, Gomes AP, Xiao CY, Palmeira CM, Rosenzweig A, and Sinclair DA. Regulation of the mPTP by SIRT3-mediated deacetylation of CypD at lysine 166 suppresses age-related cardiac hypertrophy. Aging (Albany NY) 2: 914-923, 2010.
51. Haigis MC, Deng CX, Finley LW, Kim HS, and Gius D. SIRT3 is a mitochondrial tumor suppressor: a scientific tale that connects aberrant cellular ROS, the Warburg effect, and carcinogenesis. Cancer Res 72: 2468-2472, 2012.
52. Haigis MC, Mostoslavsky R, Haigis KM, Fahie K, Christodoulou DC, Murphy AJ, Valenzuela DM, Yancopoulos GD, Karow M, Blander G, Wolberger C, Prolla TA, Weindruch R, Alt FW, and Guarente L. SIRT4 inhibits glutamate dehydrogenase and opposes the effects of calorie restriction in pancreatic beta cells. Cell 126: 941-954, 2006.
53. Hallows WC, Lee S, and Denu JM. Sirtuins deacetylate and activate mammalian acetyl-CoA synthetases. Proc Natl Acad Sci U S A 103: 10230-10235, 2006.
54. Hallows WC, Yu W, Smith BC, Devries MK, Ellinger JJ, Someya S, Shortreed MR, Prolla T, Markley JL, Smith LM, Zhao S, Guan KL, and Denu JM. Sirt3 promotes the urea cycle and fatty acid oxidation during dietary restriction. Mol Cell 41: 139-149, 2011.
55. Haussinger D. Nitrogen metabolism in liver: structural and functional organization and physiological relevance. Biochem J 267: 281-290, 1990.
56. Haynes CM and Ron D. The mitochondrial UPR - protecting organelle protein homeostasis. J Cell Sci 123: 3849-3855, 2010.
57. Hebert AS, Dittenhafer-Reed KE, Yu W, Bailey DJ, Selen ES, Boersma MD, Carson JJ, Tonelli M, Balloon AJ, Higbee AJ, Westphall MS, Pagliarini DJ, Prolla TA, Assadi-Porter F, Roy S, Denu JM, and Coon JJ. Calorie restriction and SIRT3 trigger global reprogramming of the mitochondrial protein acetylome. Mol Cell 49: 186-199, 2013.
58. Hirschey MD, Shimazu T, Goetzman E, Jing E, Schwer B, Lombard DB, Grueter CA, Harris C, Biddinger S, Ilkayeva OR, Stevens RD, Li Y, Saha AK, Ruderman NB, Bain JR, Newgard CB, Farese RV, Jr., Alt FW, Kahn CR, and Verdin E. SIRT3 regulates mitochondrial fatty-acid oxidation by reversible enzyme deacetylation. Nature 464: 121-125, 2010.
59. Hirschey MD, Shimazu T, Jing E, Grueter CA, Collins AM, Aouizerat B, Stancakova A, Goetzman E, Lam MM, Schwer B, Stevens RD, Muehlbauer MJ, Kakar S, Bass NM, Kuusisto J, Laakso M, Alt FW, Newgard CB, Farese RV, Jr., Kahn CR, and Verdin E. SIRT3 deficiency and mitochondrial protein hyperacetylation accelerate the development of the metabolic syndrome. Mol Cell 44: 177-190, 2011.
60. Hitosugi T, Fan J, Chung TW, Lythgoe K, Wang X, Xie J, Ge Q, Gu TL, Polakiewicz RD, Roesel JL, Chen GZ, Boggon TJ, Lonial S, Fu H, Khuri FR, Kang S, and Chen J. Tyrosine phosphorylation of mitochondrial pyruvate dehydrogenase kinase 1 is important for cancer metabolism. Mol Cell 44: 864-877, 2011.
61. Ho L, Titus AS, Banerjee KK, George S, Lin W, Deota S, Saha AK, Nakamura K, Gut P, Verdin E, and Kolthur-Seetharam U. SIRT4 regulates ATP homeostasis and mediates a retrograde signaling via AMPK. Aging (Albany NY) 5: 835-849, 2013.
62. Holmstrom KM and Finkel T. Cellular mechanisms and physiological consequences of redox-dependent signalling. Nat Rev Mol Cell Biol 15: 411-421, 2014.
63. Houtkooper RH, Canto C, Wanders RJ, and Auwerx J. The secret life of NAD+: an old metabolite controlling new metabolic signaling pathways. Endocr Rev 31: 194-223, 2010.
64. Hulver MW, Berggren JR, Carper MJ, Miyazaki M, Ntambi JM, Hoffman EP, Thyfault JP, Stevens R, Dohm GL, Houmard JA, and Muoio DM. Elevated stearoyl-CoA desaturase-1 expression in skeletal muscle contributes to abnormal fatty acid partitioning in obese humans. Cell Metab 2: 251-261, 2005.
65. Imai S, Armstrong CM, Kaeberlein M, and Guarente L. Transcriptional silencing and longevity protein Sir2 is an NAD-dependent histone deacetylase. Nature 403: 795-800, 2000.
66. Imai S and Guarente L. Ten years of NAD-dependent SIR2 family deacetylases: implications for metabolic diseases. Trends Pharmacol Sci 31: 212-220, 2010.
67. Inuzuka H, Gao D, Finley LW, Yang W, Wan L, Fukushima H, Chin YR, Zhai B, Shaik S, Lau AW, Wang Z, Gygi SP, Nakayama K, Teruya-Feldstein J, Toker A, Haigis MC, Pandolfi PP, and Wei W. Acetylationdependent regulation of Skp2 function. Cell 150: 179-193, 2012.
68. Iwahara T, Bonasio R, Narendra V, and Reinberg D. SIRT3 functions in the nucleus in the control of stress-related gene expression. Mol Cell Biol 32: 5022-5034, 2012.
69. Jeong SM, Lee A, Lee J, and Haigis MC. SIRT4 protein suppresses tumor formation in genetic models of Myc-induced B cell lymphoma. J Biol Chem 289: 4135-4144, 2014.
70. Jeong SM, Lee J, Finley LW, Schmidt PJ, Fleming MD, and Haigis MC. SIRT3 regulates cellular iron metabolism and cancer growth by repressing iron regulatory protein 1. Oncogene 2014 [Epub ahead of print]; DOI: 10.1038/onc.2014.124.
71. Jeong SM, Xiao C, Finley LWS, Lahusen T, Souza AL, Pierce K, Li Y-H, Wang X, Laurent G, German NJ, Xu X, Li C, Wang R-H, Lee J, Csibi A, Cerione R, Blenis J, Clish CB, Kimmelman A, Deng C-X, and Haigis MC. SIRT4 has tumor-suppressive activity and regulates the cellular metabolic response to DNA damage by inhibiting mitochondrial glutamine metabolism. Cancer Cell 23: 450-463, 2013.
72. Jiang H, Khan S, Wang Y, Charron G, He B, Sebastian C, Du J, Kim R, Ge E, Mostoslavsky R, Hang HC, Hao Q, and Lin H. SIRT6 regulates TNF-α secretion through hydrolysis of long-chain fatty acyl lysine. Nature 496: 110-113, 2013.
73. Jiang H, Talaska AE, Schacht J, and Sha SH. Oxidative imbalance in the aging inner ear. Neurobiol Aging 28: 1605-1612, 2007.
74. Jing E, O'Neill BT, Rardin MJ, Kleinridders A, Ilkeyeva OR, Ussar S, Bain JR, Lee KY, Verdin EM, Newgard CB, Gibson BW, and Kahn CR. Sirt3 regulates metabolic flexibility of skeletal muscle through reversible enzymatic deacetylation. Diabetes 62: 3404-3417, 2013.
75. Jovaisaite V, Mouchiroud L, and Auwerx J. The mitochondrial unfolded protein response, a conserved stress response pathway with implications in health and disease. J Exp Biol 217: 137-143, 2014.
76. Kaplon J, Zheng L, Meissl K, Chaneton B, Selivanov VA, Mackay G, van der Burg SH, Verdegaal EM, Cascante M, Shlomi T, Gottlieb E, and Peeper DS. A key role for mitochondrial gatekeeper pyruvate dehydrogenase in oncogene-induced senescence. Nature 498: 109-112, 2013.
77. Kendrick AA, Choudhury M, Rahman SM, McCurdy CE, Friederich M, Van Hove JL, Watson PA, Birdsey N, Bao J, Gius D, Sack MN, Jing E, Kahn CR, Friedman JE, and Jonscher KR. Fatty liver is associated with reduced SIRT3 activity and mitochondrial protein hyperacetylation. Biochem J 433: 505-514, 2011.
78. Kersten S, Seydoux J, Peters JM, Gonzalez FJ, Desvergne B, and Wahli W. Peroxisome proliferator-activated receptor alpha mediates the adaptive response to fasting. J Clin Invest 103: 1489-1498, 1999.
79. Kim HS, Patel K, Muldoon-Jacobs K, Bisht KS, Aykin-Burns N, Pennington JD, van der Meer R, Nguyen P, Savage J, Owens KM, Vassilopoulos A, Ozden O, Park SH, Singh KK, Abdulkadir SA, Spitz DR, Deng CX, and Gius D. SIRT3 is a mitochondria-localized tumor suppressor required for maintenance of mitochondrial integrity and metabolism during stress. Cancer Cell 17: 41-52, 2010.
80. Kim JW, Gao P, Liu YC, Semenza GL, and Dang CV. Hypoxia-inducible factor 1 and dysregulated c-Myc cooperatively induce vascular endothelial growth factor and metabolic switches hexokinase 2 and pyruvate dehydrogenase kinase 1. Mol Cell Biol 27: 7381-7393, 2007.
81. Kim JW, Tchernyshyov I, Semenza GL, and Dang CV. HIF-1-mediated expression of pyruvate dehydrogenase kinase: a metabolic switch required for cellular adaptation to hypoxia. Cell Metab 3: 177-185, 2006.
82. Kong X, Wang R, Xue Y, Liu X, Zhang H, Chen Y, Fang F, and Chang Y. Sirtuin 3, a new target of PGC-1alpha, plays an important role in the suppression of ROS and mitochondrial biogenesis. PLoS One 5: e11707, 2010.
83. Laurent G, de Boer VC, Finley LW, Sweeney M, Lu H, Schug TT, Cen Y, Jeong SM, Li X, Sauve AA, and Haigis MC. SIRT4 represses peroxisome proliferator-activated receptor alpha activity to suppress hepatic fat oxidation. Mol Cell Biol 33: 4552-4561, 2013.
84. Laurent G, German NJ, Saha AK, de Boer VC, Davies M, Koves TR, Dephoure N, Fischer F, Boanca G, Vaitheesvaran B, Lovitch SB, Sharpe AH, Kurland IJ, Steegborn C, Gygi SP, Muoio DM, Ruderman NB, and Haigis MC. SIRT4 coordinates the balance between lipid synthesis and catabolism by repressing malonyl CoA decarboxylase. Mol Cell 50: 686-698, 2013.
85. Leone TC, Weinheimer CJ, and Kelly DP. A critical role for the peroxisome proliferator-activated receptor alpha (PPARalpha) in the cellular fasting response: the PPAR-alpha-null mouse as a model of fatty acid oxidation disorders. Proc Natl Acad Sci U S A 96: 7473-7478, 1999.
86. Li M, Chiu JF, Mossman BT, and Fukagawa NK. Downregulation of manganese-superoxide dismutase through phosphorylation of FOXO3a by Akt in explanted vascular smooth muscle cells from old rats. J Biol Chem 281: 40429-40439, 2006.
87. Li S, Banck M, Mujtaba S, Zhou MM, Sugrue MM, and Walsh MJ. p53-induced growth arrest is regulated by the mitochondrial SirT3 deacetylase. PLoS One 5: e10486, 2010.
88. Lin ZF, Xu HB, Wang JY, Lin Q, Ruan Z, Liu FB, Jin W, Huang HH, and Chen X. SIRT5 desuccinylates and activates SOD1 to eliminate ROS. Biochem Biophys Res Commun 441: 191-195, 2013.
89. Liu B, Che W, Xue J, Zheng C, Tang K, Zhang J, Wen J, and Xu Y. SIRT4 prevents hypoxia-induced apoptosis in H9c2 cardiomyoblast cells. Cell Physiol Biochem 32: 655-662, 2013.
90. Liu XZ and Yan D. Ageing and hearing loss. J Pathol 211: 188-197, 2007.
91. Lombard DB, Alt FW, Cheng HL, Bunkenborg J, Streeper RS, Mostoslavsky R, Kim J, Yancopoulos G, Valenzuela D, Murphy A, Yang Y, Chen Y, Hirschey MD, Bronson RT, Haigis M, Guarente LP, Farese RV, Jr., Weissman S, Verdin E, and Schwer B. Mammalian Sir2 homolog SIRT3 regulates global mitochondrial lysine acetylation. Mol Cell Biol 27: 8807-8814, 2007.
92. Lombard DB, Tishkoff DX, and Bao J. Mitochondrial sirtuins in the regulation of mitochondrial activity and metabolic adaptation. Handb Exp Pharmacol 206: 163-188, 2011.
93. Lombard DB and Zwaans BM. SIRT3: as simple as it seems? Gerontology 60: 56-64, 2014.
94. Lu W, Zuo Y, Feng Y, and Zhang M. SIRT5 facilitates cancer cell growth and drug resistance in non-small cell lung cancer. Tumour Biol 35: 10699-10705, 2014.
95. Lukey MJ, Wilson KF, and Cerione RA. Therapeutic strategies impacting cancer cell glutamine metabolism. Future Med Chem 5: 1685-1700, 2013.
96. Matsushita N, Yonashiro R, Ogata Y, Sugiura A, Nagashima S, Fukuda T, Inatome R, and Yanagi S. Distinct regulation of mitochondrial localization and stability of two human Sirt5 isoforms. Genes Cells 16: 190-202, 2011.
97. Meijer AJ, Lamers WH, and Chamuleau RA. Nitrogen metabolism and ornithine cycle function. Physiol Rev 70: 701-748, 1990.
98. Meynet O and Ricci JE. Caloric restriction and cancer: molecular mechanisms and clinical implications. Trends Mol Med 20: 419-427, 2014.
99. Michishita E, Park JY, Burneskis JM, Barrett JC, and Horikawa I. Evolutionarily conserved and nonconserved cellular localizations and functions of human SIRT proteins. Mol Biol Cell 16: 4623-4635, 2005.
100. Mueller S. Iron regulatory protein 1 as a sensor of reactive oxygen species. Biofactors 24: 171-181, 2005.
101. Nakagawa T and Guarente L. Urea cycle regulation by mitochondrial sirtuin, SIRT5. Aging (Albany NY) 1: 578-581, 2009.
102. Nakagawa T, Lomb DJ, Haigis MC, and Guarente L. SIRT5 Deacetylates carbamoyl phosphate synthetase 1 and regulates the urea cycle. Cell 137: 560-570, 2009.
103. Nakamura Y, Ogura M, Ogura K, Tanaka D, and Inagaki N. SIRT5 deacetylates and activates urate oxidase in liver mitochondria of mice. FEBS Lett 586: 4076-4081, 2012.
104. Nasrin N, Wu X, Fortier E, Feng Y, Bare OC, Chen S, Ren X, Wu Z, Streeper RS, and Bordone L. SIRT4 regulates fatty acid oxidation and mitochondrial gene expression in liver and muscle cells. J Biol Chem 285: 31995-32002, 2010.
105. Nisoli E, Tonello C, Cardile A, Cozzi V, Bracale R, Tedesco L, Falcone S, Valerio A, Cantoni O, Clementi E, Moncada S, and Carruba MO. Calorie restriction promotes mitochondrial biogenesis by inducing the expression of eNOS. Science 310: 314-317, 2005.
106. Nisoli E and Valerio A. Healthspan and longevity in mammals: a family game for cellular organelles? Curr Pharm Des 20: 5663-5670, 2014.
107. North BJ, Marshall BL, Borra MT, Denu JM, and Verdin E. The human Sir2 ortholog, SIRT2, is an NAD+-dependent tubulin deacetylase. Mol Cell 11: 437-444, 2003.
108. Ogura M, Nakamura Y, Tanaka D, Zhuang X, Fujita Y, Obara A, Hamasaki A, Hosokawa M, and Inagaki N. Overexpression of SIRT5 confirms its involvement in deacetylation and activation of carbamoyl phosphate synthetase 1. Biochem Biophys Res Commun 393: 73-78, 2010.
109. Oudijk L, Gaal J, Korpershoek E, van Nederveen FH, Kelly L, Schiavon G, Verweij J, Mathijssen RH, den Bakker MA, Oldenburg RA, van Loon RL, O'Sullivan MJ, de Krijger RR, and Dinjens WN. SDHA mutations in adult and pediatric wild-type gastrointestinal stromal tumors. Mod Pathol 26: 456-463, 2013.
110. Ozden O, Park SH, Wagner BA, Song HY, Zhu Y, Vassilopoulos A, Jung B, Buettner GR, and Gius D. Sirt3 deacetylates and increases pyruvate dehydrogenase activity in cancer cells. Free Radic Biol Med 76: 163-172, 2014.
111. Palacios OM, Carmona JJ, Michan S, Chen KY, Manabe Y, Ward JL, 3rd, Goodyear LJ, and Tong Q. Diet and exercise signals regulate SIRT3 and activate AMPK and PGC-1alpha in skeletal muscle. Aging (Albany NY) 1: 771-783, 2009.
112. Papa L and Germain D. SirT3 regulates the mitochondrial unfolded protein response. Mol Cell Biol 34: 699-710, 2014.
113. Papa L, Hahn M, Marsh EL, Evans BS, and Germain D. SOD2 to SOD1 switch in breast cancer. J Biol Chem 289: 5412-5416, 2014.
114. Papa L, Manfredi G, and Germain D. SOD1, an unexpected novel target for cancer therapy. Genes Cancer 5: 15-21, 2014.
115. Papandreou I, Cairns RA, Fontana L, Lim AL, and Denko NC. HIF-1 mediates adaptation to hypoxia by actively downregulating mitochondrial oxygen consumption. Cell Metab 3: 187-197, 2006.
116. Park J, Chen Y, Tishkoff DX, Peng C, Tan M, Dai L, Xie Z, Zhang Y, Zwaans BM, Skinner ME, Lombard DB, and Zhao Y. SIRT5-mediated lysine desuccinylation impacts diverse metabolic pathways. Mol Cell 50: 919-930, 2013.
117. Patel MS and Korotchkina LG. Regulation of the pyruvate dehydrogenase complex. Biochem Soc Trans 34: 217-222, 2006.
118. Patel MS, Nemeria NS, Furey W, and Jordan F. The pyruvate dehydrogenase complexes: structure-based function and regulation. J Biol Chem 289: 16615-16623, 2014.
119. Pebay-Peyroula E and Brandolin G. Nucleotide exchange in mitochondria: insight at a molecular level. Curr Opin Struct Biol 14: 420-425, 2004.
120. Peek CB, Affinati AH, Ramsey KM, Kuo HY, Yu W, Sena LA, Ilkayeva O, Marcheva B, Kobayashi Y, Omura C, Levine DC, Bacsik DJ, Gius D, Newgard CB, Goetzman E, Chandel NS, Denu JM, Mrksich M, and Bass J. Circadian clock NAD+ cycle drives mitochondrial oxidative metabolism in mice. Science 342: 1243417, 2013.
121. Peng C, Lu Z, Xie Z, Cheng Z, Chen Y, Tan M, Luo H, Zhang Y, He W, Yang K, Zwaans BM, Tishkoff D, Ho L, Lombard D, He TC, Dai J, Verdin E, Ye Y, and Zhao Y. The first identification of lysine malonylation substrates and its regulatory enzyme. Mol Cell Proteomics 10: M111. 012658, 2011.
122. Pillai VB, Sundaresan NR, Kim G, Gupta M, Rajamohan SB, Pillai JB, Samant S, Ravindra PV, Isbatan A, and Gupta MP. Exogenous NAD blocks cardiac hypertrophic response via activation of the SIRT3-LKB1-AMP-activated kinase pathway. J Biol Chem 285: 3133-3144, 2010.
123. Pirinen E, Lo Sasso G, and Auwerx J. Mitochondrial sirtuins and metabolic homeostasis. Best Pract Res Clin Endocrinol Metab 26: 759-770, 2012.
124. Qiu X, Brown K, Hirschey MD, Verdin E, and Chen D. Calorie restriction reduces oxidative stress by SIRT3-mediated SOD2 activation. Cell Metab 12: 662-667, 2010.
125. Rahman M, Nirala NK, Singh A, Zhu LJ, Taguchi K, Bamba T, Fukusaki E, Shaw LM, Lambright DG, Acharya JK, and Acharya UR. Drosophila Sirt2/mammalian SIRT3 deacetylates ATP synthase beta and regulates complex V activity. J Cell Biol 206: 289-305, 2014.
126. Ranieri M, Brajkovic S, Riboldi G, Ronchi D, Rizzo F, Bresolin N, Corti S, and Comi GP. Mitochondrial fusion proteins and human diseases. Neurol Res Int 2013: 293893, 2013.
127. Rardin MJ, He W, Nishida Y, Newman JC, Carrico C, Danielson SR, Guo A, Gut P, Sahu AK, Li B, Uppala R, Fitch M, Riiff T, Zhu L, Zhou J, Mulhern D, Stevens RD, Ilkayeva OR, Newgard CB, Jacobson MP, Hellerstein M, Goetzman ES, Gibson BW, and Verdin E. SIRT5 regulates the mitochondrial lysine succinylome and metabolic networks. Cell Metab 18: 920-933, 2013.
128. Rardin MJ, Newman JC, Held JM, Cusack MP, Sorensen DJ, Li B, Schilling B, Mooney SD, Kahn CR, Verdin E, and Gibson BW. Label-free quantitative proteomics of the lysine acetylome in mitochondria identifies substrates of SIRT3 in metabolic pathways. Proc Natl Acad Sci U S A 110: 6601-6606, 2013.
129. Ricketts C, Woodward ER, Killick P, Morris MR, Astuti D, Latif F, and Maher ER. Germline SDHB mutations and familial renal cell carcinoma. J Natl Cancer Inst 100: 1260-1262, 2008.
130. Ricketts CJ, Forman JR, Rattenberry E, Bradshaw N, Lalloo F, Izatt L, Cole TR, Armstrong R, Kumar VK, Morrison PJ, Atkinson AB, Douglas F, Ball SG, Cook J, Srirangalingam U, Killick P, Kirby G, Aylwin S, Woodward ER, Evans DG, Hodgson SV, Murday V, Chew SL, Connell JM, Blundell TL, Macdonald F, and Maher ER. Tumor risks and genotype-phenotype-proteotype analysis in 358 patients with germline mutations in SDHB and SDHD. Hum Mutat 31: 41-51, 2010.
131. Rose G, Dato S, Altomare K, Bellizzi D, Garasto S, Greco V, Passarino G, Feraco E, Mari V, Barbi C, BonaFe M, Franceschi C, Tan Q, Boiko S, Yashin AI, and De Benedictis G. Variability of the SIRT3 gene, human silent information regulator Sir2 homologue, and survivorship in the elderly. Exp Gerontol 38: 1065-1070, 2003.
132. Sack MN. Emerging characterization of the role of SIRT3-mediated mitochondrial protein deacetylation in the heart. Am J Physiol Heart Circ Physiol 301: H2191-H2197, 2011.
133. Saggerson D. Malonyl-CoA, a key signaling molecule in mammalian cells. Annu Rev Nutr 28: 253-272, 2008.
134. Sakakibara I, Fujino T, Ishii M, Tanaka T, Shimosawa T, Miura S, Zhang W, Tokutake Y, Yamamoto J, Awano M, Iwasaki S, Motoike T, Okamura M, Inagaki T, Kita K, Ezaki O, Naito M, Kuwaki T, Chohnan S, Yamamoto TT, Hammer RE, Kodama T, Yanagisawa M, and Sakai J. Fasting-induced hypothermia and reduced energy production in mice lacking acetyl-CoA synthetase 2. Cell Metab 9: 191-202, 2009.
135. Samant SA, Zhang HJ, Hong Z, Pillai VB, Sundaresan NR, Wolfgeher D, Archer SL, Chan DC, and Gupta MP. SIRT3 deacetylates and activates OPA1 to regulate mitochondrial dynamics during stress. Mol Cell Biol 34: 807-819, 2014.
136. Schiff M, Benit P, Coulibaly A, Loublier S, El-Khoury R, and Rustin P. Mitochondrial response to controlled nutrition in health and disease. Nutr Rev 69: 65-75, 2011.
137. Schlicker C, Gertz M, Papatheodorou P, Kachholz B, Becker CF, and Steegborn C. Substrates and regulation mechanisms for the human mitochondrial sirtuins Sirt3 and Sirt5. J Mol Biol 382: 790-801, 2008.
138. Schwer B, Bunkenborg J, Verdin RO, Andersen JS, and Verdin E. Reversible lysine acetylation controls the activity of the mitochondrial enzyme acetyl-CoA synthetase 2. Proc Natl Acad Sci U S A 103: 10224-10229, 2006.
139. Schwer B, Eckersdorff M, Li Y, Silva JC, Fermin D, Kurtev MV, Giallourakis C, Comb MJ, Alt FW, and Lombard DB. Calorie restriction alters mitochondrial protein acetylation. Aging Cell 8: 604-606, 2009.
140. Schwer B, North BJ, Frye RA, Ott M, and Verdin E. The human silent information regulator (Sir)2 homologue hSIRT3 is a mitochondrial nicotinamide adenine dinucleotide-dependent deacetylase. J Cell Biol 158: 647-657, 2002.
141. Seidman MD. Effects of dietary restriction and antioxidants on presbyacusis. Laryngoscope 110: 727-738, 2000.
142. Shi T, Fan GQ, and Xiao SD. SIRT3 reduces lipid accumulation via AMPK activation in human hepatic cells. J Dig Dis 11: 55-62, 2010.
143. Shi T, Wang F, Stieren E, and Tong Q. SIRT3, a mitochondrial sirtuin deacetylase, regulates mitochondrial function and thermogenesis in brown adipocytes. J Biol Chem 280: 13560-13567, 2005.
144. Shimazu T, Hirschey MD, Hua L, Dittenhafer-Reed KE, Schwer B, Lombard DB, Li Y, Bunkenborg J, Alt FW, Denu JM, Jacobson MP, and Verdin E. SIRT3 deacetylates mitochondrial 3-hydroxy-3-methylglutaryl CoA synthase 2 and regulates ketone body production. Cell Metab 12: 654-661, 2010.
145. Shulga N, Wilson-Smith R, and Pastorino JG. Sirtuin-3 deacetylation of cyclophilin D induces dissociation of hexokinase II from the mitochondria. J Cell Sci 123: 894-902, 2010.
146. Sohal RS and Weindruch R. Oxidative stress, caloric restriction, and aging. Science 273: 59-63, 1996.
147. Sol EM, Wagner SA, Weinert BT, Kumar A, Kim HS, Deng CX, and Choudhary C. Proteomic investigations of lysine acetylation identify diverse substrates of mitochondrial deacetylase sirt3. PLoS One 7: e50545, 2012.
148. Someya S and Prolla TA. Mitochondrial oxidative damage and apoptosis in age-related hearing loss. Mech Ageing Dev 131: 480-486, 2010.
149. Someya S, Xu J, Kondo K, Ding D, Salvi RJ, Yamasoba T, Rabinovitch PS, Weindruch R, Leeuwenburgh C, Tanokura M, and Prolla TA. Age-related hearing loss in C57BL/6J mice is mediated by Bak-dependent mitochondrial apoptosis. Proc Natl Acad Sci U S A 106: 19432-19437, 2009.
150. Someya S, Yamasoba T, Weindruch R, Prolla TA, and Tanokura M. Caloric restriction suppresses apoptotic cell death in the mammalian cochlea and leads to prevention of presbycusis. Neurobiol Aging 28: 1613-1622, 2007.
151. Someya S, Yu W, Hallows WC, Xu J, Vann JM, Leeuwenburgh C, Tanokura M, Denu JM, and Prolla TA. Sirt3 mediates reduction of oxidative damage and prevention of age-related hearing loss under caloric restriction. Cell 143: 802-812, 2010.
152. Somwar R, Erdjument-Bromage H, Larsson E, Shum D, Lockwood WW, Yang G, Sander C, Ouerfelli O, Tempst PJ, Djaballah H, and Varmus HE. Superoxide dismutase 1 (SOD1) is a target for a small molecule identified in a screen for inhibitors of the growth of lung adenocarcinoma cell lines. Proc Natl Acad Sci U S A 108: 16375-16380, 2011.
153. Sundaresan NR, Gupta M, Kim G, Rajamohan SB, Isbatan A, and Gupta MP. Sirt3 blocks the cardiac hypertrophic response by augmenting Foxo3a-dependent antioxidant defense mechanisms in mice. J Clin Invest 119: 2758-2771, 2009.
154. Sundaresan NR, Samant SA, Pillai VB, Rajamohan SB, and Gupta MP. SIRT3 is a stress-responsive deacetylase in cardiomyocytes that protects cells from stress-mediated cell death by deacetylation of Ku70. Mol Cell Biol 28: 6384-6401, 2008.
155. Tan M, Luo H, Lee S, Jin F, Yang JS, Montellier E, Buchou T, Cheng Z, Rousseaux S, Rajagopal N, Lu Z, Ye Z, Zhu Q, Wysocka J, Ye Y, Khochbin S, Ren B, and Zhao Y. Identification of 67 histone marks and histone lysine crotonylation as a new type of histone modification. Cell 146: 1016-1028, 2011.
156. Tan M, Peng C, Anderson KA, Chhoy P, Xie Z, Dai L, Park J, Chen Y, Huang H, Zhang Y, Ro J, Wagner GR, Green MF, Madsen AS, Schmiesing J, Peterson BS, Xu G, Ilkayeva OR, Muehlbauer MJ, Braulke T, Muhlhausen C, Backos DS, Olsen CA, McGuire PJ, Pletcher SD, Lombard DB, Hirschey MD, and Zhao Y. Lysine glutarylation is a protein posttranslational modification regulated by SIRT5. Cell Metab 19: 605-617, 2014.
157. Tan WQ, Wang K, Lv DY, and Li PF. Foxo3a inhibits cardiomyocyte hypertrophy through transactivating catalase. J Biol Chem 283: 29730-29739, 2008.
158. Tang X, Luo YX, Chen HZ, and Liu DP. Mitochondria, endothelial cell function, and vascular diseases. Front Physiol 5: 175, 2014.
159. Tao R, Coleman MC, Pennington JD, Ozden O, Park SH, Jiang H, Kim HS, Flynn CR, Hill S, Hayes McDonald W, Olivier AK, Spitz DR, and Gius D. Sirt3-mediated deacetylation of evolutionarily conserved lysine 122 regulates MnSOD activity in response to stress. Mol Cell 40: 893-904, 2010.
160. Tiwari N, Gheldof A, Tatari M, and Christofori G. EMT as the ultimate survival mechanism of cancer cells. Semin Cancer Biol 22: 194-207, 2012.
161. Trachootham D, Alexandre J, and Huang P. Targeting cancer cells by ROS-mediated mechanisms: a radical therapeutic approach? Nat Rev Drug Discov 8: 579-591, 2009.
162. Turner N and Heilbronn LK. Is mitochondrial dysfunction a cause of insulin resistance? Trends Endocrinol Metab 19: 324-330, 2008.
163. Turrens JF. Mitochondrial formation of reactive oxygen species. J Physiol 552: 335-344, 2003.
164. Vega RB, Huss JM, and Kelly DP. The coactivator PGC-1 cooperates with peroxisome proliferator-activated receptor alpha in transcriptional control of nuclear genes encoding mitochondrial fatty acid oxidation enzymes. Mol Cell Biol 20: 1868-1876, 2000.
165. Verdin E, Hirschey MD, Finley LW, and Haigis MC. Sirtuin regulation of mitochondria: energy production, apoptosis, and signaling. Trends Biochem Sci 35: 669-675, 2010.
166. Wagner GR and Hirschey MD. Nonenzymatic protein acylation as a carbon stress regulated by sirtuin deacylases. Mol Cell 54: 5-16, 2014.
167. Wagner GR and Payne RM. 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, 2013.
168. Wahlstrom T and Arsenian Henriksson M. Impact of MYC in regulation of tumor cell metabolism. Biochim Biophys Acta 2014 [Epub ahead of print]; DOI: 10.1016/j.bbagrm.2014.07.004.
169. Wallace DC. Mitochondria and cancer. Nat Rev Cancer 12: 685-698, 2012.
170. Wang Q, Wen YG, Li DP, Xia J, Zhou CZ, Yan DW, Tang HM, and Peng ZH. Upregulated INHBA expression is associated with poor survival in gastric cancer. Med Oncol 29: 77-83, 2012.
171. Watford M. The urea cycle: a two-compartment system. Essays Biochem 26: 49-58, 1991.
172. Winder WW, Wilson HA, Hardie DG, Rasmussen BB, Hutber CA, Call GB, Clayton RD, Conley LM, Yoon S, and Zhou B. Phosphorylation of rat muscle acetyl-CoA carboxylase by AMP-activated protein kinase and protein kinase A. J Appl Physiol (1985) 82: 219-225, 1997.
173. Wu Z, Puigserver P, Andersson U, Zhang C, Adelmant G, Mootha V, Troy A, Cinti S, Lowell B, Scarpulla RC, and Spiegelman BM. Mechanisms controlling mitochondrial biogenesis and respiration through the thermogenic coactivator PGC-1. Cell 98: 115-124, 1999.
174. Yechoor VK, Patti ME, Ueki K, Laustsen PG, Saccone R, Rauniyar R, and Kahn CR. Distinct pathways of insulinregulated versus diabetes-regulated gene expression: an in vivo analysis in MIRKO mice. Proc Natl Acad Sci U S A 101: 16525-16530, 2004.
175. Yu J, Sadhukhan S, Noriega LG, Moullan N, He B, Weiss RS, Lin H, Schoonjans K, and Auwerx J. Metabolic characterization of a Sirt5 deficient mouse model. Sci Rep 3: 2806, 2013.
176. Yu W, Dittenhafer-Reed KE, and Denu JM. SIRT3 protein deacetylates isocitrate dehydrogenase 2 (IDH2) and regulates mitochondrial redox status. J Biol Chem 287: 14078-14086, 2012.
177. Zhang CZ, Liu L, Cai M, Pan Y, Fu J, Cao Y, and Yun J. Low SIRT3 expression correlates with poor differentiation and unfavorable prognosis in primary hepatocellular carcinoma. PLoS One 7: e51703, 2012.
178. Zhang YY and Zhou LM. Sirt3 inhibits hepatocellular carcinoma cell growth through reducing Mdm2-mediated p53 degradation. Biochem Biophys Res Commun 423: 26-31, 2012.
179. Zwaans BM and Lombard DB. Interplay between sirtuins, MYC and hypoxia-inducible factor in cancer-associated metabolic reprogramming. Dis Model Mech 7: 1023-1032, 2014.