Alleviation of neuronal energy deficiency by mtor inhibition as a treatment for mitochondria-related neurodegeneration

eLife

Volumn 5, Issue MARCH2016, 2016, Pages

  Zheng, Xinde ^a   Boyer, Leah ^a   Jin, Mingji ^a   Kim, Yongsung ^a   Fan, Weiwei ^a   Bardy, Cedric ^a   Berggren, Travis ^a   Evans, Ronald M ^a,b   Gage, Fred H ^a   Hunter, Tony ^a  

^a SALK INSTITUTE FOR BIOLOGICAL STUDIES   (United States)

^b HOWARD HUGHES MEDICAL INSTITUTE   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

4E1RC; ACETYL COENZYME A CARBOXYLASE; ADENOSINE TRIPHOSPHATE; ALANINE; ASPARAGINE; CALCINEURIN; CYCLOHEXIMIDE; GLUTAMIC ACID; HISTIDINE; HYDROXYMETHYLGLUTARYL COENZYME A REDUCTASE KINASE; ISOLEUCINE; LACTIC ACID; LEUCINE; MAMMALIAN TARGET OF RAPAMYCIN; METHIONINE; OLIGOMYCIN; PHENYLALANINE; PROLINE; PROTEIN S6; PROTON TRANSPORTING ADENOSINE TRIPHOSPHATE SYNTHASE; RAPAMYCIN; REACTIVE OXYGEN METABOLITE; S6 KINASE; SERINE; TACROLIMUS; UNCLASSIFIED DRUG; VALINE; MTOR PROTEIN, HUMAN; NEUROPROTECTIVE AGENT; TARGET OF RAPAMYCIN KINASE;

ARTICLE; CONTROLLED STUDY; ENZYME DEFICIENCY; FIBROBLAST; GLYCOLYSIS; HUMAN; HUMAN CELL; IMMUNOBLOTTING; IMMUNOHISTOCHEMISTRY; LEIGH DISEASE; MASS FRAGMENTOGRAPHY; MATERNALLY INHERITED LEIGH SYNDROME; METABOLITE; MITOCHONDRION; NERVE CELL; NERVE DEGENERATION; OXIDATIVE PHOSPHORYLATION; PHENOTYPE; PLURIPOTENT STEM CELL; PROTEIN PHOSPHORYLATION; PROTEIN SYNTHESIS; PROTEIN SYNTHESIS INHIBITION; REVERSE TRANSCRIPTION POLYMERASE CHAIN REACTION; ANTAGONISTS AND INHIBITORS; CELL CULTURE; DEGENERATIVE DISEASE; DRUG EFFECTS; METABOLISM; PATHOLOGY; PHYSIOLOGY;

ADENOSINE TRIPHOSPHATE; CELLS, CULTURED; HUMANS; MITOCHONDRIA; NEURODEGENERATIVE DISEASES; NEURONS; NEUROPROTECTIVE AGENTS; PROTEIN BIOSYNTHESIS; SIROLIMUS; TOR SERINE-THREONINE KINASES;

EID: 84969199737     PISSN: None     EISSN: 2050084X     Source Type: Journal    
DOI: 10.7554/eLife.13378     Document Type: Article

References (68)

1. Almeida A, Almeida J, Bolaños JP, Moncada S. 2001. Different responses of astrocytes and neurons to nitric oxide: the role of glycolytically generated ATP in astrocyte protection. Proceedings of the National Academy of Sciences of the United States of America 98:15294–15299. doi: 10.1073/pnas.261560998
2. Amato S, Liu X, Zheng B, Cantley L, Rakic P, Man HY. 2011. AMP-activated protein kinase regulates neuronal polarization by interfering with PI 3-kinase localization. Science 332:247–251. doi: 10.1126/science.1201678
3. An WL, Cowburn RF, Li L, Braak H, Alafuzoff I, Iqbal K, Iqbal IG, Winblad B, Pei JJ. 2003. Up-regulation of phosphorylated/activated p70 S6 kinase and its relationship to neurofibrillary pathology in Alzheimer’s disease. The American Journal of Pathology 163:591–607. doi: 10.1016/S0002-9440(10)63687-5
4. Bar-Peled L, Sabatini DM. 2014. Regulation of mTORC1 by amino acids. Trends in Cell Biology 24:400–406. doi: 10.1016/j.tcb.2014.03.003
5. Bové J, Martínez-Vicente M, Vila M. 2011. Fighting neurodegeneration with rapamycin: mechanistic insights. Nature Reviews. Neuroscience 12:437–452. doi: 10.1038/nrn3068
6. Brennand KJ, Simone A, Jou J, Gelboin-Burkhart C, Tran N, Sangar S, Li Y, Mu Y, Chen G, Yu D, McCarthy S, Sebat J, Gage FH. 2011. Modelling schizophrenia using human induced pluripotent stem cells. Nature 473: 221–225. doi: 10.1038/nature09915
7. Buckmaster PS, Ingram EA, Wen X. 2009. Inhibition of the mammalian target of rapamycin signaling pathway suppresses dentate granule cell axon sprouting in a rodent model of temporal lobe epilepsy. Journal of Neuroscience 29:8259–8269. doi: 10.1523/JNEUROSCI.4179-08.2009
8. Bélanger M, Allaman I, Magistretti PJ. 2011. Brain energy metabolism: focus on astrocyte-neuron metabolic cooperation. Cell Metabolism 14:724–738. doi: 10.1016/j.cmet.2011.08.016
9. Caccamo A, De Pinto V, Messina A, Branca C, Oddo S. 2014. Genetic reduction of mammalian target of rapamycin ameliorates Alzheimer’s disease-like cognitive and pathological deficits by restoring hippocampal gene expression signature. Journal of Neuroscience 34:7988–7998. doi: 10.1523/JNEUROSCI.0777-14.2014
10. Cencic R, Hall DR, Robert F, Du Y, Min J, Li L, Qui M, Lewis I, Kurtkaya S, Dingledine R, Fu H, Kozakov D, Vajda S, Pelletier J. 2011. Reversing chemoresistance by small molecule inhibition of the translation initiation complex eIF4F. Proceedings of the National Academy of Sciences of the United States of America 108:1046–1051. doi: 10.1073/pnas.1011477108
11. Cortés-Hernández P, Vázquez-Memije ME, García JJ. 2007. ATP6 homoplasmic mutations inhibit and destabilize the human F1F0-ATP synthase without preventing enzyme assembly and oligomerization. The Journal of Biological Chemistry 282:1051–1058. doi: 10.1074/jbc.M606828200
12. Dang CV. 2012. Links between metabolism and cancer. Genes & Development 26:877–890. doi: 10.1101/gad.189365.112
13. Darin N, Oldfors A, Moslemi AR, Holme E, Tulinius M. 2001. The incidence of mitochondrial encephalomyopathies in childhood: clinical features and morphological, biochemical, and DNA anbormalities. Annals of Neurology 49:377–383. doi: 10.1002/ana.75.abs
14. DeBerardinis RJ, Thompson CB. 2012. Cellular metabolism and disease: what do metabolic outliers teach us? Cell 148:1132–1144. doi: 10.1016/j.cell.2012.02.032
15. DeNicola GM, Chen P-H, Mullarky E, Sudderth JA, Hu Z, Wu D, Tang H, Xie Y, Asara JM, Huffman KE, Wistuba II, Minna JD, DeBerardinis RJ, Cantley LC. 2015. NRF2 regulates serine biosynthesis in non–small cell lung cancer. Nature Genetics 47:1475–1481. doi: 10.1038/ng.3421
16. Devi L, Prabhu BM, Galati DF, Avadhani NG, Anandatheerthavarada HK. 2006. Accumulation of amyloid precursor protein in the mitochondrial import channels of human Alzheimer’s disease brain is associated with mitochondrial dysfunction. Journal of Neuroscience 26:9057–9068. doi: 10.1523/JNEUROSCI.1469-06.2006
17. Fan J, Ye J, Kamphorst JJ, Shlomi T, Thompson CB, Rabinowitz JD. 2014. Quantitative flux analysis reveals folate-dependent NADPH production. Nature 510:298–302. doi: 10.1038/nature13236
18. Finsterer J. 2008. Leigh and Leigh-like syndrome in children and adults. Pediatric Neurology 39:223–235. doi: 10.1016/j.pediatrneurol.2008.07.013
19. Greenwood SM, Mizielinska SM, Frenguelli BG, Harvey J, Connolly CN. 2007. Mitochondrial dysfunction and dendritic beading during neuronal toxicity. The Journal of Biological Chemistry 282:26235–26244. doi: 10.1074/jbc.M704488200
20. Gwinn DM, Shackelford DB, Egan DF, Mihaylova MM, Mery A, Vasquez DS, Turk BE, Shaw RJ. 2008. AMPK phosphorylation of raptor mediates a metabolic checkpoint. Molecular Cell 30:214–226. doi: 10.1016/j.molcel.2008.03.003
21. Hara K, Yonezawa K, Weng QP, Kozlowski MT, Belham C, Avruch J. 1998. Amino acid sufficiency and mTOR regulate p70 S6 kinase and eIF-4E BP1 through a common effector mechanism. The Journal of Biological Chemistry 273:14484–14494 doi: 10.1074/jbc.273.23.14484. doi: 10.1074/jbc.273.23.14484
22. Hsu PP, Kang SA, Rameseder J, Zhang Y, Ottina KA, Lim D, Peterson TR, Choi Y, Gray NS, Yaffe MB, Marto JA, Sabatini DM. 2011. The mTOR-regulated phosphoproteome reveals a mechanism of mTORC1-mediated inhibition of growth factor signaling. Science 332:1317–13122. doi: 10.1126/science.1199498
23. Inoki K, Zhu T, Guan KL. 2003. TSC2 mediates cellular energy response to control cell growth and survival. Cell 115:577–590 doi: 10.1016/S0092-8674(03)00929-2. doi: 10.1016/S0092-8674(03)00929-2
24. Johnson SC, Rabinovitch PS, Kaeberlein M. 2013a. mTOR is a key modulator of ageing and age-related disease. Nature 493:338–345. doi: 10.1038/nature11861
25. Johnson SC, Yanos ME, Kayser EB, Quintana A, Sangesland M, Castanza A, Uhde L, Hui J, Wall VZ, Gagnidze A, Oh K, Wasko BM, Ramos FJ, Palmiter RD, Rabinovitch PS, Morgan PG, Sedensky MM, Kaeberlein M. 2013b. mTOR inhibition alleviates mitochondrial disease in a mouse model of Leigh syndrome. Science 342:1524–1528. doi: 10.1126/science.1244360
26. Jonckheere AI, Renkema GH, Bras M, van den Heuvel LP, Hoischen A, Gilissen C, Nabuurs SB, Huynen MA, de Vries MC, Smeitink JA, Rodenburg RJ. 2013. A complex V ATP5A1 defect causes fatal neonatal mitochondrial encephalopathy. Brain 136:1544–1554. doi: 10.1093/brain/awt086
27. Kamp F, Exner N, Lutz AK, Wender N, Hegermann J, Brunner B, Nuscher B, Bartels T, Giese A, Beyer K, Eimer S, Winklhofer KF, Haass C. 2010. Inhibition of mitochondrial fusion by a-synuclein is rescued by PINK1, Parkin and DJ-1. The EMBO Journal 29:3571–3589. doi: 10.1038/emboj.2010.223
28. Kim D, Fiske BP, Birsoy K, Freinkman E, Kami K, Possemato RL, Chudnovsky Y, Pacold ME, Chen WW, Cantor JR, Shelton LM, Gui DY, Kwon M, Ramkissoon SH, Ligon KL, Kang SW, Snuderl M, Vander Heiden MG, Sabatini DM. 2015. SHMT2 drives glioma cell survival in ischaemia but imposes a dependence on glycine clearance. Nature 520:363–367. doi: 10.1038/nature14363
29. Laplante M, Sabatini DM. 2012. mTOR signaling in growth control and disease. Cell 149:274–293. doi: 10.1016/j.cell.2012.03.017
30. Lewis CA, Parker SJ, Fiske BP, McCloskey D, Gui DY, Green CR, Vokes NI, Feist AM, Vander Heiden MG, Metallo CM. 2014. Tracing compartmentalized NADPH metabolism in the cytosol and mitochondria of mammalian cells. Molecular Cell 55:253–263. doi: 10.1016/j.molcel.2014.05.008
31. Lin MT, Beal MF. 2006. Mitochondrial dysfunction and oxidative stress in neurodegenerative diseases. Nature 443:787–795. doi: 10.1038/nature05292
32. Lipton JO, Sahin M. 2014. The neurology of mTOR. Neuron 84:275–291. doi: 10.1016/j.neuron.2014.09.034
33. Ma H, Folmes CD, Wu J, Morey R, Mora-Castilla S, Ocampo A, Ma L, Poulton J, Wang X, Ahmed R, Kang E, Lee Y, Hayama T, Li Y, Van Dyken C, Gutierrez NM, Tippner-Hedges R, Koski A, Mitalipov N, Amato P, et al. 2015. Metabolic rescue in pluripotent cells from patients with mtDNA disease. Nature 524:234–238. doi: 10.1038/nature14546
34. Malagelada C, Jin ZH, Jackson-Lewis V, Przedborski S, Greene LA. 2010. Rapamycin protects against neuron death in in vitro and in vivo models of Parkinson’s disease. Journal of Neuroscience 30:1166–1175. doi: 10.1523/JNEUROSCI.3944-09.2010
35. Manfredi G, Gupta N, Vazquez-Memije ME, Sadlock JE, Spinazzola A, De Vivo DC, Schon EA. 1999. Oligomycin induces a decrease in the cellular content of a pathogenic mutation in the human mitochondrial ATPase 6 gene. The Journal of Biological Chemistry 274:9386–9391 doi: 10.1074/jbc.274.14.9386. doi: 10.1074/jbc.274.14.9386
36. Martin I, Kim JW, Lee BD, Kang HC, Xu JC, Jia H, Stankowski J, Kim MS, Zhong J, Kumar M, Andrabi SA, Xiong Y, Dickson DW, Wszolek ZK, Pandey A, Dawson TM, Dawson VL. 2014. Ribosomal protein s15 phosphorylation mediates LRRK2 neurodegeneration in Parkinson’s disease. Cell 157:472–485. doi: 10.1016/j.cell.2014.01.064
37. Martínez-Reyes I, Chandel NS. 2014. Mitochondrial one-carbon metabolism maintains redox balance during hypoxia. Cancer Discovery 4:1371–1373. doi: 10.1158/2159-8290.CD-14-1228
38. Mattiazzi M, Vijayvergiya C, Gajewski CD, DeVivo DC, Lenaz G, Wiedmann M, Manfredi G. 2004. The mtDNA T8993G (NARP) mutation results in an impairment of oxidative phosphorylation that can be improved by antioxidants. Human Molecular Genetics 13:869–879. doi: 10.1093/hmg/ddh103
39. Murphy TH, Miyamoto M, Sastre A, Schnaar RL, Coyle JT. 1989. Glutamate toxicity in a neuronal cell line involves inhibition of cystine transport leading to oxidative stress. Neuron 2:1547–1558 doi: 10.1016/0896-6273(89)90043-3. doi: 10.1016/0896-6273(89)90043-3
40. Nakai N, Kawano F, Nakata K. 2015. Mechanical stretch activates mammalian target of rapamycin and AMP-activated protein kinase pathways in skeletal muscle cells. Molecular and Cellular Biochemistry 406:285–292. doi: 10.1007/s11010-015-2446-7
41. Nakamura K, Nemani VM, Azarbal F, Skibinski G, Levy JM, Egami K, Munishkina L, Zhang J, Gardner B, Wakabayashi J, Sesaki H, Cheng Y, Finkbeiner S, Nussbaum RL, Masliah E, Edwards RH. 2011. Direct membrane association drives mitochondrial fission by the Parkinson disease-associated protein alpha-synuclein. The Journal of Biological Chemistry 286:20710–20726. doi: 10.1074/jbc.M110.213538
42. Ng TL, Leprivier G, Robertson MD, Chow C, Martin MJ, Laderoute KR, Davicioni E, Triche TJ, Sorensen PH. 2012. The AMPK stress response pathway mediates anoikis resistance through inhibition of mTOR and suppression of protein synthesis. Cell Death and Differentiation 19:501–510. doi: 10.1038/cdd.2011.119
43. Nicholls DG, Johnson-Cadwell L, Vesce S, Jekabsons M, Yadava N. 2007. Bioenergetics of mitochondria in cultured neurons and their role in glutamate excitotoxicity. Journal of Neuroscience Research 85:3206–3212. doi: 10.1002/jnr.21290
44. Pastores GM, Santorelli FM, Shanske S, Gelb BD, Fyfe B, Wolfe D, Willner JP. 1994. Leigh syndrome and hypertrophic cardiomyopathy in an infant with a mitochondrial DNA point mutation (T8993G). American Journal of Medical Genetics 50:265–271. doi: 10.1002/ajmg.1320500310
45. Pickrell AM, Youle RJ. 2015. The roles of PINK1, parkin, and mitochondrial fidelity in Parkinson’s disease. Neuron 85:257–273. doi: 10.1016/j.neuron.2014.12.007
46. Pinto M, Moraes CT. 2014. Mitochondrial genome changes and neurodegenerative diseases. Biochimica Et Biophysica Acta 1842:1198–1207. doi: 10.1016/j.bbadis.2013.11.012
47. Porto FB, Mack G, Sterboul MJ, Lewin P, Flament J, Sahel J, Dollfus H. 2001. Isolated late-onset cone-rod dystrophy revealing a familial neurogenic muscle weakness, ataxia, and retinitis pigmentosa syndrome with the T8993G mitochondrial mutation. American Journal of Ophthalmology 132:935–937 doi: 10.1016/S0002-9394(01)01187-4. doi: 10.1016/S0002-9394(01)01187-4
48. Qiang L, Fujita R, Abeliovich A. 2013. Remodeling neurodegeneration: somatic cell reprogramming-based models of adult neurological disorders. Neuron 78:957–969. doi: 10.1016/j.neuron.2013.06.002
49. Rolfe DF, Brown GC. 1997. Cellular energy utilization and molecular origin of standard metabolic rate in mammals. Physiological Reviews 77:731–758.
50. Rothman SM. 1985. The neurotoxicity of excitatory amino acids is produced by passive chloride influx. Journal of Neuroscience 5:1483–1489.
51. Sancak Y, Thoreen CC, Peterson TR, Lindquist RA, Kang SA, Spooner E, Carr SA, Sabatini DM. 2007. PRAS40 is an insulin-regulated inhibitor of the mTORC1 protein kinase. Molecular Cell 25:903–915. doi: 10.1016/j.molcel.2007.03.003
52. Scott DA, Richardson AD, Filipp FV, Knutzen CA, Chiang GG, Ronai ZA, Osterman AL, Smith JW. 2011. Comparative metabolic flux profiling of melanoma cell lines: beyond the Warburg effect. Journal of Biological Chemistry 286:42626–42634. doi: 10.1074/jbc.M111.282046
53. Stryer L, Berg JM, Tymoczko JL. 2002. Biochemistry. 5th ed. New York: W H Freeman.
54. Tain LS, Mortiboys H, Tao RN, Ziviani E, Bandmann O, Whitworth AJ. 2009. Rapamycin activation of 4E-BP prevents parkinsonian dopaminergic neuron loss. Nature Neuroscience 12:1129–1135. doi: 10.1038/nn.2372
55. Takahashi K, Tanabe K, Ohnuki M, Narita M, Ichisaka T, Tomoda K, Yamanaka S. 2007. Induction of pluripotent stem cells from adult human fibroblasts by defined factors. Cell 131:861–872. doi: 10.1016/j.cell.2007.11.019
56. Takeuchi H, Mizuno T, Zhang G, Wang J, Kawanokuchi J, Kuno R, Suzumura A. 2005. Neuritic beading induced by activated microglia is an early feature of neuronal dysfunction toward neuronal death by inhibition of mitochondrial respiration and axonal transport. The Journal of Biological Chemistry 280:10444–10454. doi: 10.1074/jbc.M413863200
57. Tantama M, Martínez-François JR, Mongeon R, Yellen G. 2013. Imaging energy status in live cells with a fluorescent biosensor of the intracellular ATP-to-ADP ratio. Nature Communications 4:2550. doi: 10.1038/ncomms3550
58. Taylor AL, Watson CJ, Bradley JA. 2005. Immunosuppressive agents in solid organ transplantation: Mechanisms of action and therapeutic efficacy. Critical Reviews in Oncology/hematology 56:23–46. doi: 10.1016/j.critrevonc.2005.03.012
59. Taylor RW, Turnbull DM. 2005. Mitochondrial DNA mutations in human disease. Nature Reviews. Genetics 6: 389–402. doi: 10.1038/nrg1606
60. Thoreen CC, Chantranupong L, Keys HR, Wang T, Gray NS, Sabatini DM. 2012. A unifying model for mTORC1-mediated regulation of mRNA translation. Nature 485:109–113. doi: 10.1038/nature11083
61. Trounce I, Neill S, Wallace DC. 1994. Cytoplasmic transfer of the mtDNA nt 8993 T–>G (ATP6) point mutation associated with Leigh syndrome into mtDNA-less cells demonstrates cosegregation with a decrease in state III respiration and ADP/O ratio. Proceedings of the National Academy of Sciences of the United States of America 91:8334–8338. doi: 10.1073/pnas.91.18.8334
62. Uziel G, Moroni I, Lamantea E, Fratta GM, Ciceri E, Carrara F, Zeviani M. 1997. Mitochondrial disease associated with the T8993G mutation of the mitochondrial ATPase 6 gene: a clinical, biochemical, and molecular study in six families. Journal of Neurology, Neurosurgery, and Psychiatry 63:16–22. doi: 10.1136/jnnp.63.1.16
63. Vafai SB, Mootha VK. 2013. Medicine. A common pathway for a rare disease? Science 342:1453–1454. doi: 10.1126/science.1248449
64. Vander Haar E, Lee SI, Bandhakavi S, Griffin TJ, Kim DH. 2007. Insulin signalling to mTOR mediated by the Akt/ PKB substrate PRAS40. Nature Cell Biology 9:316–323. doi: 10.1038/ncb1547
65. Wang X, Chen XJ. 2015. A cytosolic network suppressing mitochondria-mediated proteostatic stress and cell death. Nature 524:481–484. doi: 10.1038/nature14859
66. Ye J, Fan J, Venneti S, Wan YW, Pawel BR, Zhang J, Finley LW, Lu C, Lindsten T, Cross JR, Qing G, Liu Z, Simon MC, Rabinowitz JD, Thompson CB. 2014. Serine catabolism regulates mitochondrial redox control during hypoxia. Cancer Discovery 4:1406–1417. doi: 10.1158/2159-8290.CD-14-0250
67. Zoncu R, Efeyan A, Sabatini DM. 2011. mTOR: from growth signal integration to cancer, diabetes and ageing. Nature Reviews. Molecular Cell Biology 12:21–35. doi: 10.1038/nrm3025
68. Zuccato C, Valenza M, Cattaneo E. 2010. Molecular mechanisms and potential therapeutical targets in Huntington’s disease. Physiological Reviews 90:905–981. doi: 10.1152/physrev.00041.2009