Extranuclear localization of SIRT1 and PGC-1α: An insight into possible roles in diseases associated with mitochondrial dysfunction

Current Molecular Medicine

Volumn 13, Issue 1, 2013, Pages 140-154

  Aquilano, K ^a   Baldelli, S ^a   Pagliei, B ^a   Ciriolo, M R ^a,b  

^a UNIVERSITY OF ROME TOR VERGATA   (Italy)

^b IRCCS SAN RAFFAELE PISANA   (Italy)

Author keywords

Biogenesis; Cellular metabolism; Cytoplasm; Mitochondria; Mitochondrial diseases; Transcriptional regulation

Indexed keywords

COPPER ZINC SUPEROXIDE DISMUTASE; ESTROGEN RELATED RECEPTOR ALPHA; GA BINDING PROTEIN; GLUTATHIONE PEROXIDASE; HEPATOCYTE NUCLEAR FACTOR 1ALPHA; HISTONE H4; HYDROXYMETHYLGLUTARYL COENZYME A REDUCTASE KINASE; INSULIN RECEPTOR SUBSTRATE 2; MAMMALIAN TARGET OF RAPAMYCIN COMPLEX 1; MANGANESE SUPEROXIDE DISMUTASE; MITOCHONDRIAL DNA; MITOGEN ACTIVATED PROTEIN KINASE KINASE 4; MITOGEN ACTIVATED PROTEIN KINASE P38; NUCLEAR RESPIRATORY FACTOR 1; PEROXISOME PROLIFERATOR ACTIVATED RECEPTOR GAMMA COACTIVATOR 1ALPHA; SIRTUIN 1; SIRTUIN 6; TRANSCRIPTION FACTOR FKHR; HEAT SHOCK PROTEIN; PPARGC1A PROTEIN, HUMAN; SIRT1 PROTEIN, HUMAN; TRANSCRIPTION FACTOR;

ALZHEIMER DISEASE; AMYOTROPHIC LATERAL SCLEROSIS; DEGENERATIVE DISEASE; DISORDERS OF MITOCHONDRIAL FUNCTIONS; DNA TRANSCRIPTION; FRIEDREICH ATAXIA; GLUCOSE TRANSPORT; HUMAN; HUNTINGTON CHOREA; MYOPATHY; NON INSULIN DEPENDENT DIABETES MELLITUS; NUCLEAR LOCALIZATION SIGNAL; PARKINSON DISEASE; PROTEIN LOCALIZATION; REVIEW; WESTERN BLOTTING; CELL NUCLEUS; CYTOPLASM; GENETICS; METABOLISM; MITOCHONDRION;

CELL NUCLEUS; CYTOPLASM; DIABETES MELLITUS, TYPE 2; HEAT-SHOCK PROTEINS; HUMANS; MITOCHONDRIA; MITOCHONDRIAL DISEASES; NEURODEGENERATIVE DISEASES; SIRTUIN 1; TRANSCRIPTION FACTORS;

EID: 84878941111     PISSN: 15665240     EISSN: 18755666     Source Type: Journal    
DOI: 10.2174/156652413804486241     Document Type: Review

References (136)

1. Rigoulet M, Yoboue ED, Devin A. Mitochondrial ROS Generation and Its Regulation: Mechanisms Involved in H(2)O(2) Signaling. Antioxid Redox Signal 2010; 14(3): 459-68.
2. Falkenberg M, Larsson NG, Gustafsson CM. DNA replication and transcription in mammalian mitochondria. Annu Rev Biochem 2007; 76: 679-99.
3. Hock MB, Kralli A. Transcriptional control of mitochondrial biogenesis and function. Annu Rev Physiol 2009; 71: 177-203.
4. Canto C, Auwerx J. PGC-1alpha, SIRT1 and AMPK, an energy sensing network that controls energy expenditure. Curr Opin Lipidol 2009; 20: 98-105.
5. Canto C, Gerhart-Hines Z, Feige JN, et al. AMPK regulates energy expenditure by modulating NAD+ metabolism and SIRT1 activity. Nature 2009; 458: 1056-60.
6. Yi J, Luo J. SIRT1 and p53, effect on cancer, senescence and beyond. Biochim Biophys Acta 2010; 1804: 1684-9.
7. Giannakou ME, Partridge L. The interaction between FOXO and SIRT1: tipping the balance towards survival. Trends Cell Biol 2004; 14: 408-12.
8. Park SH, Gammon SR, Knippers JD, Paulsen SR, Rubink DS, Winder WW. Phosphorylation-activity relationships of AMPK and acetyl-CoA carboxylase in muscle. J Appl Physiol 2002; 92: 2475-82.
9. Ojuka EO, Jones TE, Nolte LA, et al. Regulation of GLUT4 biogenesis in muscle: evidence for involvement of AMPK and Ca(2+). Am J Physiol Endocrinol Metab 2002; 282: E1008-13.
10. Rodgers JT, Lerin C, Gerhart-Hines Z, Puigserver P. Metabolic adaptations through the PGC-1 alpha and SIRT1 pathways. FEBS Lett 2008; 582: 46-53.
11. Nemoto S, Fergusson MM, Finkel T. SIRT1 functionally interacts with the metabolic regulator and transcriptional coactivator PGC-1{alpha}. J Biol Chem 2005; 280: 16456-60.
12. Lee WJ, Kim M, Park HS, et al. AMPK activation increases fatty acid oxidation in skeletal muscle by activating PPARalpha and PGC-1. Biochem Biophys Res Commun 2006; 340: 291-5.
13. Finkel T. Cell biology: a clean energy programme. Nature 2006; 444: 151-2.
14. Gleyzer N, Vercauteren K, Scarpulla RC. Control of mitochondrial transcription specificity factors (TFB1M and TFB2M) by nuclear respiratory factors (NRF-1 and NRF-2) and PGC-1 family coactivators. Mol Cell Biol 2005; 25: 1354-66.
15. Wang Y, Bogenhagen DF. Human mitochondrial DNA nucleoids are linked to protein folding machinery and metabolic enzymes at the mitochondrial inner membrane. J Biol Chem 2006; 281: 25791-802.
16. Kang D, Kim SH, Hamasaki N. Mitochondrial transcription factor A (TFAM): roles in maintenance of mtDNA and cellular functions. Mitochondrion 2007; 7: 39-44.
17. Puigserver P, Wu Z, Park CW, Graves R, Wright M, Spiegelman BM. A cold-inducible coactivator of nuclear receptors linked to adaptive thermogenesis. Cell 1998; 92: 829-39.
18. Lin J, Handschin C, Spiegelman BM. Metabolic control through the PGC-1 family of transcription coactivators. Cell Metab 2005; 1: 361-70.
19. Scarpulla RC. Transcriptional paradigms in mammalian mitochondrial biogenesis and function. Physiol Rev 2008; 88: 611-38.
20. Scarpulla RC. Metabolic control of mitochondrial biogenesis through the PGC-1 family regulatory network. Biochim Biophys Acta 2010; 1813(7): 1269-78.
21. Matsumoto M, Pocai A, Rossetti L, Depinho RA, Accili D. Impaired regulation of hepatic glucose production in mice lacking the forkhead transcription factor Foxo1 in liver. Cell Metab 2007; 6: 208-16.
22. Handschin C, Spiegelman BM. PGC-1 coactivators and the regulation of skeletal muscle fiber-type determination. Cell Metab 2011; 13: 351; author reply 2.
23. Liang H, Ward WF. PGC-1alpha: a key regulator of energy metabolism. Adv Physiol Educ 2006; 30: 145-51.
24. St-Pierre J, Lin J, Krauss S, et al. Bioenergetic analysis of peroxisome proliferator-activated receptor gamma coactivators 1alpha and 1beta (PGC-1alpha and PGC-1beta) in muscle cells. J Biol Chem 2003; 278: 26597-603.
25. St-Pierre J, Drori S, Uldry M, et al. Suppression of reactive oxygen species and neurodegeneration by the PGC-1 transcriptional coactivators. Cell 2006; 127: 397-408.
26. Glass CK, Rosenfeld MG. The coregulator exchange in transcriptional functions of nuclear receptors. Genes Dev 2000; 14: 121-41.
27. Vega RB, Huss JM, 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 2000; 20: 1868-76.
28. Handschin C, Spiegelman BM. Peroxisome proliferator-activated receptor gamma coactivator 1 coactivators, energy homeostasis, and metabolism. Endocr Rev 2006; 27: 728-35.
29. Cunningham JT, Rodgers JT, Arlow DH, Vazquez F, Mootha VK, Puigserver P. mTOR controls mitochondrial oxidative function through a YY1-PGC-1alpha transcriptional complex. Nature 2007; 450: 736-40.
30. Puigserver P, Rhee J, Donovan J, et al. Insulin-regulated hepatic gluconeogenesis through FOXO1-PGC-1alpha interaction. Nature 2003; 423: 550-5.
31. Michael LF, Wu Z, Cheatham RB, et al. Restoration of insulin-sensitive glucose transporter (GLUT4) gene expression in muscle cells by the transcriptional coactivator PGC-1. Proc Natl Acad Sci USA 2001; 98: 3820-5.
32. Kelly TJ, Lerin C, Haas W, Gygi SP, Puigserver P. GCN5-mediated transcriptional control of the metabolic coactivator PGC-1beta through lysine acetylation. J Biol Chem 2009; 284: 19945-52.
33. Lerin C, Rodgers JT, Kalume DE, Kim SH, Pandey A, Puigserver P. GCN5 acetyltransferase complex controls glucose metabolism through transcriptional repression of PGC-1alpha. Cell Metab 2006; 3: 429-38.
34. Kamei Y, Ohizumi H, Fujitani Y, et al. PPARgamma coactivator 1beta/ERR ligand 1 is an ERR protein ligand, whose expression induces a high-energy expenditure and antagonizes obesity. Proc Natl Acad Sci USA 2003; 100: 12378-83.
35. Suliman HB, Welty-Wolf KE, Carraway M, Tatro L, Piantadosi CA. Lipopolysaccharide induces oxidative cardiac mitochondrial damage and biogenesis. Cardiovasc Res 2004; 64: 279-88.
36. Wright LE, Brandon AE, Hoy AJ, et al. Amelioration of lipid-induced insulin resistance in rat skeletal muscle by overexpression of Pgc-1beta involves reductions in long- chain acyl-CoA levels and oxidative stress. Diabetologia 2011; 54(6): 1417-26.
37. Le Pennec S, Mirebeau-Prunier D, Boutet-Bouzamondo N, et al. Nitric oxide and calcium participate in the fine regulation of mitochondrial biogenesis in follicular thyroid carcinoma cells. J Biol Chem 2011; 286(20): 18229-39.
38. Raharijaona M, Le Pennec S, Poirier J, et al. PGC-1-related coactivator modulates mitochondrial-nuclear crosstalk through endogenous nitric oxide in a cellular model of oncocytic thyroid tumours. PLoS One 2009; 4: e7964.
39. Kaeberlein M, McVey M, Guarente L. The SIR2/3/4 complex and SIR2 alone promote longevity in Saccharomyces cerevisiae by two different mechanisms. Genes Dev 1999; 13: 2570-80.
40. Haigis MC, Sinclair DA. Mammalian sirtuins: biological insights and disease relevance. Annu Rev Pathol 2010; 5: 253-95.
41. Frye RA. Characterization of five human cDNAs with homology to the yeast SIR2 gene: Sir2-like proteins (sirtuins) metabolize NAD and may have protein ADP-ribosyltransferase activity. Biochem Biophys Res Commun 1999; 260: 273-9.
42. Borra MT, Denu JM. Quantitative assays for characterization of the Sir2 family of NAD(+)-dependent deacetylases. Methods Enzymol 2004; 376: 171-87.
43. Liszt G, Ford E, Kurtev M, Guarente L. Mouse Sir2 homolog SIRT6 is a nuclear ADP-ribosyltransferase. J Biol Chem 2005; 280: 21313-20.
44. Ahuja N, Schwer B, Carobbio S, et al. Regulation of insulin secretion by SIRT4, a mitochondrial ADP-ribosyltransferase. J Biol Chem 2007; 282: 33583-92.
45. Tanner KG, Landry J, Sternglanz R, Denu JM. Silent information regulator 2 family of NAD-dependent histone/protein deacetylases generates a unique product, 1-O-acetyl-ADP-ribose. Proc Natl Acad Sci USA 2000; 97: 14178-82.
46. Du J, Jiang H, Lin H. Investigating the ADP-ribosyltransferase activity of sirtuins with NAD analogues and 32P-NAD. Biochemistry 2009; 48: 2878-90.
47. Aquilano K, Vigilanza P, Baldelli S, Pagliei B, Rotilio G, Ciriolo MR. Peroxisome proliferator-activated receptor gamma co-activator 1alpha (PGC-1alpha) and sirtuin 1 (SIRT1) reside in mitochondria: possible direct function in mitochondrial biogenesis. J Biol Chem 2010; 285: 21590-9.
48. North BJ, Marshall BL, Borra MT, Denu JM, Verdin E. The human Sir2 ortholog, SIRT2, is an NAD+-dependent tubulin deacetylase. Mol Cell 2003; 11: 437-44.
49. Inoue T, Hiratsuka M, Osaki M, Oshimura M. The molecular biology of mammalian SIRT proteins: SIRT2 in cell cycle regulation. Cell Cycle 2007; 6: 1011-8.
50. Wang F, Nguyen M, Qin FX, Tong Q. SIRT2 deacetylates FOXO3a in response to oxidative stress and caloric restriction. Aging Cell 2007; 6: 505-14.
51. Schwer B, Bunkenborg J, Verdin RO, Andersen JS, Verdin E. Reversible lysine acetylation controls the activity of the mitochondrial enzyme acetyl-CoA synthetase 2. Proc Natl Acad Sci USA 2006; 103: 10224-9.
52. Lombard DB, Alt FW, Cheng HL, et al. Mammalian Sir2 homolog SIRT3 regulates global mitochondrial lysine acetylation. Mol Cell Biol 2007; 27: 8807-14.
53. Ahn BH, Kim HS, Song S, et al. A role for the mitochondrial deacetylase Sirt3 in regulating energy homeostasis. Proc Natl Acad Sci USA 2008; 105: 14447-52.
54. Ford E, Voit R, Liszt G, Magin C, Grummt I, Guarente L. Mammalian Sir2 homolog SIRT7 is an activator of RNA polymerase I transcription. Genes Dev 2006; 20: 1075-80.
55. Mostoslavsky R, Chua KF, Lombard DB, et al. Genomic instability and aging-like phenotype in the absence of mammalian SIRT6. Cell 2006; 124: 315-29.
56. Finkel T, Deng CX, Mostoslavsky R. Recent progress in the biology and physiology of sirtuins. Nature 2009; 460: 587-91.
57. Yuan Z, Seto E. A functional link between SIRT1 deacetylase and NBS1 in DNA damage response. Cell Cycle 2007; 6: 2869-71.
58. Jeong J, Juhn K, Lee H, et al. SIRT1 promotes DNA repair activity and deacetylation of Ku70. Exp Mol Med 2007; 39: 8-13.
59. Vaquero A. The conserved role of sirtuins in chromatin regulation. Int J Dev Biol 2009; 53: 303-22.
60. Vaquero A, Scher M, Lee D, Erdjument-Bromage H, Tempst P, Reinberg D. Human SirT1 interacts with histone H1 and promotes formation of facultative heterochromatin. Mol Cell 2004; 16: 93-105.
61. Brunet A, Sweeney LB, Sturgill JF, et al. Stress-dependent regulation of FOXO transcription factors by the SIRT1 deacetylase. Science 2004; 303: 2011-5.
62. Solomon JM, Pasupuleti R, Xu L, et al. Inhibition of SIRT1 catalytic activity increases p53 acetylation but does not alter cell survival following DNA damage. Mol Cell Biol 2006; 26: 28-38.
63. Yeung F, Hoberg JE, Ramsey CS, et al. Modulation of NF-kappaB-dependent transcription and cell survival by the SIRT1 deacetylase. EMBO J 2004; 23: 2369-80.
64. Bordone L, Cohen D, Robinson A, et al. SIRT1 transgenic mice show phenotypes resembling calorie restriction. Aging Cell 2007; 6: 759-67.
65. Liang F, Kume S, Koya D. SIRT1 and insulin resistance. Nat Rev Endocrinol 2009; 5: 367-73.
66. Pfluger PT, Herranz D, Velasco-Miguel S, Serrano M, Tschop MH. Sirt1 protects against high-fat diet-induced metabolic damage. Proc Natl Acad Sci USA 2008; 105: 9793-8.
67. Moynihan KA, Grimm AA, Plueger MM, et al. Increased dosage of mammalian Sir2 in pancreatic beta cells enhances glucose-stimulated insulin secretion in mice. Cell Metab 2005; 2: 105-17.
68. Bordone L, Guarente L. Calorie restriction, SIRT1 and metabolism: understanding longevity. Nat Rev Mol Cell Biol 2005; 6: 298-305.
69. Picard F, Kurtev M, Chung N, et al. Sirt1 promotes fat mobilization in white adipocytes by repressing PPAR- gamma. Nature 2004; 429: 771-6.
70. Tanno M, Sakamoto J, Miura T, Shimamoto K, Horio Y. Nucleocytoplasmic shuttling of the NAD+-dependent histone deacetylase SIRT1. J Biol Chem 2007; 282: 6823-32.
71. Hisahara S, Chiba S, Matsumoto H, et al. Histone deacetylase SIRT1 modulates neuronal differentiation by its nuclear translocation. Proc Natl Acad Sci USA 2008; 105: 15599-604.
72. Sugino T, Maruyama M, Tanno M, Kuno A, Houkin K, Horio Y. Protein deacetylase SIRT1 in the cytoplasm promotes nerve growth factor-induced neurite outgrowth in PC12 cells. FEBS Lett 2010; 584: 2821-6.
73. Hou J, Chong ZZ, Shang YC, Maiese K. Early apoptotic vascular signaling is determined by Sirt1 through nuclear shuttling, forkhead trafficking, bad, and mitochondrial caspase activation. Curr Neurovasc Res 2010; 7: 95-112.
74. Jin Q, Yan T, Ge X, Sun C, Shi X, Zhai Q. Cytoplasm-localized SIRT1 enhances apoptosis. J Cell Physiol 2007; 213: 88-97.
75. Tanno M, Kuno A, Yano T, et al. Induction of manganese superoxide dismutase by nuclear translocation and activation of SIRT1 promotes cell survival in chronic heart failure. J Biol Chem 2010; 285: 8375-82.
76. Nasrin N, Kaushik VK, Fortier E, et al. JNK1 phosphorylates SIRT1 and promotes its enzymatic activity. PLoS One 2009; 4: e8414.
77. Andersen JL, Thompson JW, Lindblom KR, et al. A biotin switch-based proteomics approach identifies 14-3-3zeta as a target of sirt1 in the metabolic regulation of caspase-2. Mol Cell 2011; 43: 834-42.
78. Byles V, Chmilewski LK, Wang J, et al. Aberrant cytoplasm localization and protein stability of SIRT1 is regulated by PI3K/IGF-1R signaling in human cancer cells. Int J Biol Sci 2010; 6: 599-612.
79. Zhang J. The direct involvement of SirT1 in insulin-induced insulin receptor substrate-2 tyrosine phosphorylation. J Biol Chem 2007; 282: 34356-64.
80. Law IK, Liu L, Xu A, et al. Identification and characterization of proteins interacting with SIRT1 and SIRT3: implications in the anti-aging and metabolic effects of sirtuins. Proteomics 2009; 9: 2444-56.
81. Zhang Y, Zhang M, Dong H, et al. Deacetylation of cortactin by SIRT1 promotes cell migration. Oncogene 2009; 28: 445-60.
82. Kim D, Nguyen MD, Dobbin MM, et al. SIRT1 deacetylase protects against neurodegeneration in models for Alzheimer's disease and amyotrophic lateral sclerosis. EMBO J 2007; 26: 3169-79.
83. Lee IH, Cao L, Mostoslavsky R, et al. A role for the NAD-dependent deacetylase Sirt1 in the regulation of autophagy. Proc Natl Acad Sci USA 2008; 105: 3374-9.
84. Wright DC, Han DH, Garcia-Roves PM, Geiger PC, Jones TE, Holloszy JO. Exercise-induced mitochondrial biogenesis begins before the increase in muscle PGC-1alpha expression. J Biol Chem 2007; 282: 194-9.
85. Little JP, Safdar A, Cermak N, Tarnopolsky MA, Gibala MJ. Acute endurance exercise increases the nuclear abundance of PGC-1alpha in trained human skeletal muscle. Am J Physiol Regul Integr Comp Physiol 2010; 298: R912-7.
86. Anderson RM, Barger JL, Edwards MG, et al. Dynamic regulation of PGC-1alpha localization and turnover implicates mitochondrial adaptation in calorie restriction and the stress response. Aging Cell 2008; 7: 101-11.
87. Trausch-Azar J, Leone TC, Kelly DP, Schwartz AL. Ubiquitin proteasome-dependent degradation of the transcriptional coactivator PGC-1{alpha} via the N-terminal pathway. J Biol Chem 2010; 285: 40192-200.
88. Soriano FX, Liesa M, Bach D, Chan DC, Palacin M, Zorzano A. Evidence for a mitochondrial regulatory pathway defined by peroxisome proliferator-activated receptor-gamma coactivator-1 alpha, estrogen-related receptor-alpha, and mitofusin 2. Diabetes 2006; 55: 1783-91.
89. Stunkel W, Peh BK, Tan YC, et al. Function of the SIRT1 protein deacetylase in cancer. Biotechnol J 2007; 2: 1360-8.
90. Mochel F, Haller RG. Energy deficit in Huntington disease: why it matters. J Clin Invest 2011; 121: 493-9.
91. Reddy PH, Mao P, Manczak M. Mitochondrial structural and functional dynamics in Huntington's disease. Brain Res Rev 2009; 61: 33-48.
92. Acevedo-Torres K, Berrios L, Rosario N, et al. Mitochondrial DNA damage is a hallmark of chemically induced and the R6/2 transgenic model of Huntington's disease. DNA Repair (Amst) 2009; 8: 126-36.
93. Zheng B, Liao Z, Locascio JJ, et al. PGC-1alpha, a potential therapeutic target for early intervention in Parkinson's disease. Sci Transl Med 2010; 2: 52ra73.
94. Clark J, Simon DK. Transcribe to survive: transcriptional control of antioxidant defense programs for neuroprotection in Parkinson's disease. Antioxid Redox Signal 2009; 11: 509-28.
95. Hardingham GE, Lipton SA. Regulation of neuronal oxidative and nitrosative stress by endogenous protective pathways and disease processes. Antioxid Redox Signal 2011; 14: 1421-4.
96. Chao J, Yu MS, Ho YS, Wang M, Chang RC. Dietary oxyresveratrol prevents parkinsonian mimetic 6-hydroxydopamine neurotoxicity. Free Radic Biol Med 2008; 45: 1019-26.
97. Albani D, Polito L, Batelli S, et al. The SIRT1 activator resveratrol protects SK-N-BE cells from oxidative stress and against toxicity caused by alpha-synuclein or amyloid-beta (1-42) peptide. J Neurochem 2009; 110: 1445-56.
98. Pallas M, Pizarro JG, Gutierrez-Cuesta J, et al. Modulation of SIRT1 expression in different neurodegenerative models and human pathologies. Neuroscience 2008; 154: 1388-97.
99. Esteves AR, Lu J, Rodova M, et al. Mitochondrial respiration and respiration-associated proteins in cell lines created through Parkinson's subject mitochondrial transfer. J Neurochem 2010; 113: 674-82.
100. Pacelli C, De Rasmo D, Signorile A, et al. Mitochondrial defect and PGC-1alpha dysfunction in parkin-associated familial Parkinson's disease. Biochim Biophys Acta 2011; 1812(8): 1041-53.
101. Shin JH, Ko HS, Kang H, et al. PARIS (ZNF746) repression of PGC-1alpha contributes to neurodegeneration in Parkinson's disease. Cell 2011; 144: 689-702.
102. Bonda DJ, Lee HG, Camins A, et al. The sirtuin pathway in ageing and Alzheimer disease: mechanistic and therapeutic considerations. Lancet Neurol 2011; 10: 275-9.
103. Donmez G, Wang D, Cohen DE, Guarente L. SIRT1 suppresses beta-amyloid production by activating the alpha- secretase gene ADAM10. Cell 2010; 142: 320-32.
104. Albani D, Polito L, Forloni G. Sirtuins as novel targets for Alzheimer's disease and other neurodegenerative disorders: experimental and genetic evidence. J Alzheimers Dis 2010; 19: 11-26.
105. Campuzano V, Montermini L, Lutz Y, et al. Frataxin is reduced in Friedreich ataxia patients and is associated with mitochondrial membranes. Hum Mol Genet 1997; 6: 1771-80.
106. Coppola G, Marmolino D, Lu D, et al. Functional genomic analysis of frataxin deficiency reveals tissue-specific alterations and identifies the PPARgamma pathway as a therapeutic target in Friedreich's ataxia. Hum Mol Genet 2009; 18: 2452-61.
107. Marmolino D, Acquaviva F. Friedreich's Ataxia: from the (GAA)n repeat mediated silencing to new promising molecules for therapy. Cerebellum 2009; 8: 245-59.
108. Marmolino D, Manto M, Acquaviva F, et al. PGC-1alpha down-regulation affects the antioxidant response in Friedreich's ataxia. PLoS One 2010; 5: e10025.
109. Kiaei M, Kipiani K, Chen J, Calingasan NY, Beal MF. Peroxisome proliferator-activated receptor-gamma agonist extends survival in transgenic mouse model of amyotrophic lateral sclerosis. Exp Neurol 2005; 191: 331-6.
110. Schutz B, Reimann J, Dumitrescu-Ozimek L, et al. The oral antidiabetic pioglitazone protects from neurodegeneration and amyotrophic lateral sclerosis-like symptoms in superoxide dismutase-G93A transgenic mice. J Neurosci 2005; 25: 7805-12.
111. Liang H, Ward WF, Jang YC, et al. PGC-1alpha protects neurons and alters disease progression in an amyotrophic lateral sclerosis mouse model. Muscle Nerve 2011; 44: 947-56.
112. Zhao W, Varghese M, Yemul S, et al. Peroxisome proliferator activator receptor gamma coactivator-1alpha (PGC-1alpha) improves motor performance and survival in a mouse model of amyotrophic lateral sclerosis. Mol Neurodegener 2011; 6: 51.
113. Ylikallio E, Suomalainen A. Mechanisms of mitochondrial diseases. Annals of medicine 2012; 44: 41-59.
114. Wenz T, Diaz F, Spiegelman BM, Moraes CT. Activation of the PPAR/PGC-1alpha pathway prevents a bioenergetic deficit and effectively improves a mitochondrial myopathy phenotype. Cell Metab 2008; 8: 249-56.
115. Wenz T, Diaz F, Hernandez D, Moraes CT. Endurance exercise is protective for mice with mitochondrial myopathy. J Appl Physiol 2009; 106: 1712-9.
116. Romanino K, Mazelin L, Albert V, et al. Myopathy caused by mammalian target of rapamycin complex 1 (mTORC1) inactivation is not reversed by restoring mitochondrial function. Proc Natl Acad Sci USA 2011; 108: 20808-13.
117. Takikita S, Schreiner C, Baum R, et al. Fiber type conversion by PGC-1alpha activates lysosomal and autophagosomal biogenesis in both unaffected and Pompe skeletal muscle. PLoS One 2010; 5: e15239.
118. Wenz T, Rossi SG, Rotundo RL, Spiegelman BM, Moraes CT. Increased muscle PGC-1alpha expression protects from sarcopenia and metabolic disease during aging. Proc Natl Acad Sci USA 2009; 106: 20405-10.
119. Miura S, Tomitsuka E, Kamei Y, et al. Overexpression of peroxisome proliferator-activated receptor gamma co-activator-1alpha leads to muscle atrophy with depletion of ATP. Am J Pathol 2006; 169: 1129-39.
120. Price NL, Gomes AP, Ling AJ, et al. SIRT1 Is Required for AMPK Activation and the Beneficial Effects of Resveratrol on Mitochondrial Function. Cell Metab 2012; 15: 675-90.
121. Ma ZA, Zhao Z, Turk J. Mitochondrial dysfunction and beta-cell failure in type 2 diabetes mellitus. Exp Diabetes Res 2012; 2012: 703538.
122. Wiederkehr A, Wollheim CB. Mitochondrial signals drive insulin secretion in the pancreatic beta-cell. Mol Cell Endocrinol 2012; 353: 128-37.
123. Maassen JA, Jansen JJ, Kadowaki T, van den Ouweland JM, 't Hart LM, Lemkes HH. The molecular basis and clinical characteristics of Maternally Inherited Diabetes and Deafness (MIDD), a recently recognized diabetic subtype. Exp Clin Endocrinol Diabetes 1996; 104: 205-11.
124. Patti ME, Corvera S. The role of mitochondria in the pathogenesis of type 2 diabetes. Endocr Rev 2010; 31: 364-95.
125. Mootha VK, Lindgren CM, Eriksson KF, et al. PGC-1alpharesponsive genes involved in oxidative phosphorylation are coordinately downregulated in human diabetes. Nat Genet 2003; 34: 267-73.
126. Zorzano A, Hernandez-Alvarez MI, Palacin M, Mingrone G. Alterations in the mitochondrial regulatory pathways constituted by the nuclear co-factors PGC-1alpha or PGC-1beta and mitofusin 2 in skeletal muscle in type 2 diabetes. Biochim Biophys Acta 2010; 1797: 1028-33.
127. Roberts-Wilson TK, Reddy RN, Bailey JL, et al. Calcineurin signaling and PGC-1alpha expression are suppressed during muscle atrophy due to diabetes. Biochim Biophys Acta 2010; 1803: 960-7.
128. Lumini JA, Magalhaes J, Oliveira PJ, Ascensao A. Beneficial effects of exercise on muscle mitochondrial function in diabetes mellitus. Sports Med 2008; 38: 735-50.
129. Lagouge M, Argmann C, Gerhart-Hines Z, et al. Resveratrol improves mitochondrial function and protects against metabolic disease by activating SIRT1 and PGC-1alpha. Cell 2006; 127: 1109-22.
130. Joseph AM, Joanisse DR, Baillot RG, Hood DA. Mitochondrial dysregulation in the pathogenesis of diabetes: potential for mitochondrial biogenesis-mediated interventions. Experimental diabetes research 2012; 2012: 642038.
131. Kleiner S, Mepani RJ, Laznik D, et al. Development of insulin resistance in mice lacking PGC-1alpha in adipose tissues. Proc Natl Acad Sci USA 2012; 109(24): 9635-40.
132. Yamamoto A, Simonsen A. The elimination of accumulated and aggregated proteins: a role for aggrephagy in neurodegeneration. Neurobiol Dis 2011; 43: 17-28.
133. Tan L, Yu JT, Guan HS. Resveratrol exerts pharmacological preconditioning by activating PGC-1alpha. Med Hypotheses 2008; 71: 664-7.
134. Stunkel W, Campbell RM. Sirtuin 1 (SIRT1): The Misunderstood HDAC. J Biomol Screen 2011; 16(10): 1153-69.
135. Beher D, Wu J, Cumine S, et al. Resveratrol is not a direct activator of SIRT1 enzyme activity. Chem Biol Drug Des 2009; 74: 619-24.
136. Kiaei M. Peroxisome Proliferator-Activated Receptor-gamma in Amyotrophic Lateral Sclerosis and Huntington's Disease. PPAR Res 2008; 2008: 418765.