Mitochondrial biogenesis in health and disease. Molecular and therapeutic approaches

Current Pharmaceutical Design

Volumn 20, Issue 35, 2014, Pages 5619-5633

  Sanchis Gomar, Fabian ^a   García Giménez, José Luis ^a,b   Gómez Cabrera, Mari Carmen ^a   Pallardó, Federico V ^a,b  

^a UNIVERSITY OF VALENCIA   (Spain)

^b CENTRO DE INVESTIGACIÓN BIOMÉDICA EN RED DE ENFERMEDADES RARAS CIBERER   (Spain)

Author keywords

Aging; Cardiac diseases; Metabolic syndrome; Neurodegenerative diseases; Renal diseases; Sarcopenia

Indexed keywords

ADENYLATE KINASE; CYCLIC AMP; CYCLIC AMP RESPONSIVE ELEMENT BINDING PROTEIN; ESTROGEN RECEPTOR; ESTROGEN RELATED RECEPTOR ALPHA; ESTROGEN RELATED RECEPTOR BETA; ESTROGEN RELATED RECEPTOR GAMMA; NEU DIFFERENTIATION FACTOR; NITRIC OXIDE; NUCLEAR RESPIRATORY FACTOR; PARKIN; PEROXISOME PROLIFERATOR ACTIVATED RECEPTOR ALPHA; PEROXISOME PROLIFERATOR ACTIVATED RECEPTOR DELTA; PEROXISOME PROLIFERATOR ACTIVATED RECEPTOR GAMMA; PEROXISOME PROLIFERATOR ACTIVATED RECEPTOR GAMMA COACTIVATOR 1ALPHA; PEROXISOME PROLIFERATOR ACTIVATED RECEPTOR GAMMA COACTIVATOR 1BETA; PHOSPHATIDYLINOSITOL 3,4,5 TRISPHOSPHATE 3 PHOSPHATASE; POLYCOMB GROUP PROTEIN; RECEPTOR INTERACTING PROTEIN 140; SIRTUIN 1; UNCLASSIFIED DRUG; TRANSCRIPTION FACTOR;

AGING; ARTICLE; BIOGENESIS; CARDIOVASCULAR DISEASE; DEGENERATIVE DISEASE; DIABETES MELLITUS; DISORDERS OF MITOCHONDRIAL FUNCTIONS; EVIDENCE BASED PRACTICE; FRIEDREICH ATAXIA; HUMAN; HUNTINGTON CHOREA; INTRACELLULAR SIGNALING; KIDNEY DISEASE; METABOLIC SYNDROME X; MITOCHONDRIAL BIOGENESIS; MITOCHONDRION; OBESITY; PARKINSON DISEASE; PRIORITY JOURNAL; SARCOPENIA; ANIMAL; DRUG EFFECTS; ENERGY METABOLISM; HEALTH STATUS; METABOLISM; MITOCHONDRIAL DISEASES; PHYSIOLOGY; SIGNAL TRANSDUCTION;

ANIMALS; ENERGY METABOLISM; HEALTH STATUS; HUMANS; MITOCHONDRIA; MITOCHONDRIAL DISEASES; SIGNAL TRANSDUCTION; TRANSCRIPTION FACTORS;

EID: 84922513466     PISSN: 13816128     EISSN: 18734286     Source Type: Journal    
DOI: 10.2174/1381612820666140306095106     Document Type: Article

References (244)

1. [1] Hock MB, Kralli A. Transcriptional control of mitochondrial biogenesis and function. Annu Rev Physiol 2009; 71: 177-203.
2. [2] Tormos KV, Anso E, Hamanaka RB, et al. Mitochondrial complex III ROS regulate adipocyte differentiation. Cell Metab 2011; 14: 537-44.
3. [3] Hood DA. Invited Review: contractile activity-induced mitochondrial biogenesis in skeletal muscle. J Appl Physiol 2001; 90: 1137-57.
4. [4] Osellame LD, Blacker TS, Duchen MR. Cellular and molecular mechanisms of mitochondrial function. Best Pract Res Clin Endocrinol Metab 2012; 26: 711-23.
5. [5] Hales KG, Fuller MT. Developmentally regulated mitochondrial fusion mediated by a conserved, novel, predicted GTPase. Cell 1997; 90: 121-9.
6. [6] Diaz F, Moraes CT. Mitochondrial biogenesis and turnover. Cell Calcium 2008; 44: 24-35.
7. [7] Papanicolaou KN, Phillippo MM, Walsh K. Mitofusins and the mitochondrial permeability transition: the potential downside of mitochondrial fusion. Am J Physiol Heart Circ Physiol 2012; 303: H243-55.
8. [8] Wright DC, Han DH, Garcia-Roves PM, et al. Exercise-induced mitochondrial biogenesis begins before the increase in muscle PGC-1alpha expression. J Biol Chem 2007; 282: 194-9.
9. [9] Ryan MT, Hoogenraad NJ. Mitochondrial-nuclear communications. Annu Rev Biochem 2007; 76: 701-22.
10. [10] Fernandez-Marcos PJ, Auwerx J. Regulation of PGC-1alpha, a nodal regulator of mitochondrial biogenesis. Am J Clin Nutr 2011; 93: 884S-90.
11. [11] Gerhart-Hines Z, Rodgers JT, Bare O, et al. Metabolic control of muscle mitochondrial function and fatty acid oxidation through SIRT1/PGC-1alpha. Embo J 2007; 26: 1913-23.
12. [12] Teyssier C, Ma H, Emter R, Kralli A, Stallcup MR. Activation of nuclear receptor coactivator PGC-1alpha by arginine methylation. Genes Dev 2005; 19: 1466-73.
13. [13] Olson BL, Hock MB, Ekholm-Reed S, et al. SCFCdc4 acts antagonistically to the PGC-1alpha transcriptional coactivator by targeting it for ubiquitin-mediated proteolysis. Genes Dev 2008; 22: 252-64.
14. [14] Piantadosi CA. Regulation of mitochondrial processes by protein S-nitrosylation. Biochim Biophys Acta 2012; 1820: 712-21.
15. [15] Finsterer J. Mitochondriopathies. Eur J Neurol 2004; 11: 163-86.
16. [16] Stefano GB, Kim C, Mantione K, Casares F, Kream RM. Targeting mitochondrial biogenesis for promoting health. Med Sci Monit 2012; 18: SC1-3.
17. [17] Hancock CR, Han DH, Higashida K, Kim SH, Holloszy JO. Does calorie restriction induce mitochondrial biogenesis? A reevaluation. FASEB J 2011; 25: 785-91.
18. [18] Holloszy JO. Biochemical adaptations in muscle. Effects of exercise on mitochondrial oxygen uptake and respiratory enzyme activity in skeletal muscle. J Biol Chem 1967; 242: 2278-82.
19. [19] Klingenspor M. Cold-induced recruitment of brown adipose tissue thermogenesis. Exp Physiol 2003; 88: 141-8.
20. [20] Legros F, Malka F, Frachon P, Lombes A, Rojo M. Organization and dynamics of human mitochondrial DNA. J Cell Sci 2004; 117: 2653-62.
21. [21] Puigserver P, Wu Z, Park CW, et al. A cold-inducible coactivator of nuclear receptors linked to adaptive thermogenesis. Cell 1998; 92: 829-39.
22. [22] Handschin C, Spiegelman BM. Peroxisome proliferator-activated receptor gamma coactivator 1 coactivators, energy homeostasis, and metabolism. Endocr Rev 2006; 27: 728-35.
23. [23] Scarpulla RC. Transcriptional paradigms in mammalian mitochondrial biogenesis and function. Physiol Rev 2008; 88: 611-38.
24. [24] Virbasius CA, Virbasius JV, Scarpulla RC. NRF-1, an activator involved in nuclear-mitochondrial interactions, utilizes a new DNA-binding domain conserved in a family of developmental regulators. Genes Dev 1993; 7: 2431-45.
25. [25] Cam H, Balciunaite E, Blais A, et al. A common set of gene regulatory networks links metabolism and growth inhibition. Mol Cell 2004; 16: 399-411.
26. [26] Huo L, Scarpulla RC. Mitochondrial DNA instability and periimplantation lethality associated with targeted disruption of nuclear respiratory factor 1 in mice. Mol Cell Biol 2001; 21: 644-54.
27. [27] Baar K, Song Z, Semenkovich CF, et al. Skeletal muscle overexpression of nuclear respiratory factor 1 increases glucose transport capacity. Faseb J 2003; 17: 1666-73.
28. [28] Virbasius JV, Virbasius CA, Scarpulla RC. Identity of GABP with NRF-2, a multisubunit activator of cytochrome oxidase expression, reveals a cellular role for an ETS domain activator of viral promoters. Genes Dev 1993; 7: 380-92.
29. [29] Evans RM, Barish GD, Wang YX. PPARs and the complex journey to obesity. Nat Med 2004; 10: 355-61.
30. [30] Kallen J, Schlaeppi JM, Bitsch F, et al. Evidence for ligandindependent transcriptional activation of the human estrogenrelated receptor alpha (ERRalpha): crystal structure of ERRalpha ligand binding domain in complex with peroxisome proliferatoractivated receptor coactivator-1alpha. J Biol Chem 2004; 279: 49330-7.
31. [31] Giguere V. Transcriptional control of energy homeostasis by the estrogen-related receptors. Endocr Rev 2008; 29: 677-96.
32. [32] Herzig S, Long F, Jhala US, et al. CREB regulates hepatic gluconeogenesis through the coactivator PGC-1. Nature 2001; 413: 179-83.
33. [33] Khatib SY, Farah H, El-Migdadi F. Allopurinol enhances adenine nucleotide levels and improves myocardial function in isolated hypoxic rat heart. Biochemistry (Mosc) 2001; 66: 328-33.
34. [34] Zhang H, Gao P, Fukuda R, et al. HIF-1 inhibits mitochondrial biogenesis and cellular respiration in VHL-deficient renal cell carcinoma by repression of C-MYC activity. Cancer Cell 2007; 11: 407-20.
35. [35] Powelka AM, Seth A, Virbasius JV, et al. Suppression of oxidative metabolism and mitochondrial biogenesis by the transcriptional corepressor RIP140 in mouse adipocytes. J Clin Invest 2006; 116: 125-36.
36. [36] Leonardsson G, Steel JH, Christian M, et al. Nuclear receptor corepressor RIP140 regulates fat accumulation. Proc Natl Acad Sci U S A 2004; 101: 8437-42.
37. [37] Seth A, Steel JH, Nichol D, et al. The transcriptional corepressor RIP140 regulates oxidative metabolism in skeletal muscle. Cell Metab 2007; 6: 236-45.
38. [38] Rockl KS, Witczak CA, Goodyear LJ. Signaling mechanisms in skeletal muscle: acute responses and chronic adaptations to exercise. IUBMB Life 2008; 60: 145-53.
39. [39] Wu H, Kanatous SB, Thurmond FA, et al. Regulation of mitochondrial biogenesis in skeletal muscle by CaMK. Science 2002; 296: 349-52.
40. [40] Narkar VA, Downes M, Yu RT, et al. AMPK and PPARdelta agonists are exercise mimetics. Cell 2008; 134: 405-15.
41. [41] Jager S, Handschin C, St-Pierre J, Spiegelman BM. AMP-activated protein kinase (AMPK) action in skeletal muscle via direct phosphorylation of PGC-1alpha. Proc Natl Acad Sci U S A 2007; 104: 12017-22.
42. [42] Irrcher I, Adhihetty PJ, Joseph AM, Ljubicic V, Hood DA. Regulation of mitochondrial biogenesis in muscle by endurance exercise. Sports Med 2003; 33: 783-93.
43. [43] Robinson DM, Ogilvie RW, Tullson PC, Terjung RL. Increased peak oxygen consumption of trained muscle requires increased electron flux capacity. J Appl Physiol 1994; 77: 1941-52.
44. [44] 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.
45. [45] Miura S, Kawanaka K, Kai Y, et al. An increase in murine skeletal muscle peroxisome proliferator-activated receptor-gamma coactivator-1alpha (PGC-1alpha) mRNA in response to exercise is mediated by beta-adrenergic receptor activation. Endocrinology 2007; 148: 3441-8.
46. [46] Ariazi EA, Kraus RJ, Farrell ML, Jordan VC, Mertz JE. Estrogenrelated receptor alpha1 transcriptional activities are regulated in part via the ErbB2/HER2 signaling pathway. Mol Cancer Res 2007; 5: 71-85.
47. [47] Gomez-Cabrera MC, Domenech E, Romagnoli M, et al. Oral administration of vitamin C decreases muscle mitochondrial biogenesis and hampers training-induced adaptations in endurance performance. Am J Clin Nutr 2008; 87: 142-9.
48. [48] Ristow M, Zarse K, Oberbach A, et al. Antioxidants prevent health-promoting effects of physical exercise in humans. Proc Natl Acad Sci U S A 2009; 106: 8665-70.
49. [49] Nisoli E, Tonello C, Cardile A, et al. Calorie restriction promotes mitochondrial biogenesis by inducing the expression of eNOS. Science 2005; 310: 314-7.
50. [50] Foster MW, Stamler JS. New insights into protein S-nitrosylation. Mitochondria as a model system. J Biol Chem 2004; 279: 25891-7.
51. [51] Brown GC. Regulation of mitochondrial respiration by nitric oxide inhibition of cytochrome c oxidase. Biochim Biophys Acta 2001; 1504: 46-57.
52. [52] Drapier JC. Interplay between NO and [Fe-S] clusters: relevance to biological systems. Methods 1997; 11: 319-29.
53. [53] Ghafourifar P, Schenk U, Klein SD, Richter C. Mitochondrial nitric-oxide synthase stimulation causes cytochrome c release from isolated mitochondria. Evidence for intramitochondrial peroxynitrite formation. J Biol Chem 1999; 274: 31185-8.
54. [54] Mannick JB, Hausladen A, Liu L, et al. Fas-induced caspase denitrosylation. Science 1999; 284: 651-4.
55. [55] Nisoli E, Carruba MO. Nitric oxide and mitochondrial biogenesis. J Cell Sci 2006; 119: 2855-62.
56. [56] Nisoli E, Clementi E, Paolucci C, et al. Mitochondrial biogenesis in mammals: the role of endogenous nitric oxide. Science 2003; 299: 896-9.
57. [57] Kelly DP, Scarpulla RC. Transcriptional regulatory circuits controlling mitochondrial biogenesis and function. Genes Dev 2004; 18: 357-68.
58. [58] Nakamura T, Lipton SA. S-nitrosylation of critical protein thiols mediates protein misfolding and mitochondrial dysfunction in neurodegenerative diseases. Antioxid Redox Signal 2011; 14: 1479-92.
59. [59] Hord NG. Dietary nitrates, nitrites, and cardiovascular disease. Curr Atheroscler Rep 2011; 13: 484-92.
60. [60] Evans MJ, Scarpulla RC. Interaction of nuclear factors with multiple sites in the somatic cytochrome c promoter. Characterization of upstream NRF-1, ATF, and intron Sp1 recognition sequences. J Biol Chem 1989; 264: 14361-8.
61. [61] Li R, Luciakova K, Nelson BD. Expression of the human cytochrome c1 gene is controlled through multiple Sp1-binding sites and an initiator region. Eur J Biochem 1996; 241: 649-56.
62. [62] Zaid A, Li R, Luciakova K, et al. On the role of the general transcription factor Sp1 in the activation and repression of diverse mammalian oxidative phosphorylation genes. J Bioenerg Biomembr 1999; 31: 129-35.
63. [63] Kraft CS, LeMoine CM, Lyons CN, et al. Control of mitochondrial biogenesis during myogenesis. Am J Physiol Cell Physiol 2006; 290: C1119-27.
64. [64] Choi YS, Lee HK, Pak YK. Characterization of the 5'-flanking region of the rat gene for mitochondrial transcription factor A (Tfam). Biochim Biophys Acta 2002; 1574: 200-4.
65. [65] Chhunchha B, Fatma N, Bhargavan B, et al. Specificity protein, Sp1-mediated increased expression of Prdx6 as a curcumin-induced antioxidant defense in lens epithelial cells against oxidative stress. Cell Death Dis 2011; 2: e234.
66. [66] Kuo JJ, Chang HH, Tsai TH, Lee TY. Positive effect of curcumin on inflammation and mitochondrial dysfunction in obese mice with liver steatosis. Int J Mol Med 2012; 30: 673-9.
67. [67] Kuroda Y, Mitsui T, Kunishige M, et al. Parkin enhances mitochondrial biogenesis in proliferating cells. Hum Mol Genet 2006; 15: 883-95.
68. [68] Tanaka A, Cleland MM, Xu S, et al. Proteasome and p97 mediate mitophagy and degradation of mitofusins induced by Parkin. J Cell Biol 2010; 191: 1367-80.
69. [69] Narendra D, Tanaka A, Suen DF, Youle RJ. Parkin is recruited selectively to impaired mitochondria and promotes their autophagy. J Cell Biol 2008; 183: 795-803.
70. [70] Gegg ME, Cooper JM, Schapira AH, Taanman JW. Silencing of PINK1 expression affects mitochondrial DNA and oxidative phosphorylation in dopaminergic cells. PLoS One 2009; 4: e4756.
71. [71] Mai S, Klinkenberg M, Auburger G, Bereiter-Hahn J, Jendrach M. Decreased expression of Drp1 and Fis1 mediates mitochondrial elongation in senescent cells and enhances resistance to oxidative stress through PINK1. J Cell Sci 2010; 123: 917-26.
72. [72] Gandhi S, Wood-Kaczmar A, Yao Z, et al. PINK1-associated Parkinson's disease is caused by neuronal vulnerability to calciuminduced cell death. Mol Cell 2009; 33: 627-38.
73. [73] Gispert S, Ricciardi F, Kurz A, et al. Parkinson phenotype in aged PINK1-deficient mice is accompanied by progressive mitochondrial dysfunction in absence of neurodegeneration. PLoS One 2009; 4: e5777.
74. [74] Narendra DP, Jin SM, Tanaka A, et al. PINK1 is selectively stabilized on impaired mitochondria to activate Parkin. PLoS Biol 2010; 8: e1000298.
75. [75] Vives-Bauza C, Zhou C, Huang Y, et al. PINK1-dependent recruitment of Parkin to mitochondria in mitophagy. Proc Natl Acad Sci U S A; 107: 378-83.
76. [76] Garcia-Gimenez JL, Gimeno A, Gonzalez-Cabo P, et al. Differential expression of PGC-1alpha and metabolic sensors suggest agedependent induction of mitochondrial biogenesis in Friedreich ataxia fibroblasts. PLoS One 2012; 6: e20666.
77. [77] Romanello V, Guadagnin E, Gomes L, et al. Mitochondrial fission and remodelling contributes to muscle atrophy. EMBO J 2010; 29: 1774-85.
78. [78] Garcia-Gimenez JL, Gimeno A, Gonzalez-Cabo P, et al. Differential expression of PGC-1alpha and metabolic sensors suggest agedependent induction of mitochondrial biogenesis in Friedreich ataxia fibroblasts. PLoS One 2011; 6: e20666.
79. [79] Campuzano V, Montermini L, Molto MD, et al. Friedreich's ataxia: autosomal recessive disease caused by an intronic GAA triplet repeat expansion. Science 1996; 271: 1423-7.
80. [80] 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.
81. [81] Durr A, Cossee M, Agid Y, et al. Clinical and genetic abnormalities in patients with Friedreich's ataxia. N Engl J Med 1996; 335: 1169-75.
82. [82] 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.
83. [83] A novel gene containing a trinucleotide repeat that is expanded and unstable on Huntington's disease chromosomes. The Huntington's Disease Collaborative Research Group. Cell 1993; 72: 971-83.
84. [84] Weydt P, Soyal SM, Gellera C, et al. The gene coding for PGC-1alpha modifies age at onset in Huntington's Disease. Mol Neurodegener 2009; 4: 3.
85. [85] Taherzadeh-Fard E, Saft C, Andrich J, Wieczorek S, Arning L. PGC-1alpha as modifier of onset age in Huntington disease. Mol Neurodegener 2009; 4: 10.
86. [86] Arning L, Haghikia A, Taherzadeh-Fard E, et al. Mitochondrial haplogroup H correlates with ATP levels and age at onset in Huntington disease. J Mol Med (Berl) 2010; 88: 431-6.
87. [87] Che HV, Metzger S, Portal E, et al. Localization of sequence variations in PGC-1alpha influence their modifying effect in Huntington disease. Mol Neurodegener 2011; 6: 1.
88. [88] Cui L, Jeong H, Borovecki F, et al. Transcriptional repression of PGC-1alpha by mutant huntingtin leads to mitochondrial dysfunction and neurodegeneration. Cell 2006; 127: 59-69.
89. [89] Weydt P, Pineda VV, Torrence AE, et al. Thermoregulatory and metabolic defects in Huntington's disease transgenic mice implicate PGC-1alpha in Huntington's disease neurodegeneration. Cell Metab 2006; 4: 349-62.
90. [90] Chaturvedi RK, Adhihetty P, Shukla S, et al. Impaired PGC-1alpha function in muscle in Huntington's disease. Hum Mol Genet 2009; 18: 3048-65.
91. [91] Rona-Voros K, Weydt P. The Role of PGC-1alpha in the Pathogenesis of Neurodegenerative Disorders. Curr Drug Targets 2010.
92. [92] Taherzadeh-Fard E, Saft C, Akkad DA, et al. PGC-1alpha downstream transcription factors NRF-1 and TFAM are genetic modifiers of Huntington disease. Mol Neurodegener 2011; 6: 32.
93. [93] Dunah AW, Jeong H, Griffin A, et al. Sp1 and TAFII130 transcriptional activity disrupted in early Huntington's disease. Science 2002; 296: 2238-43.
94. [94] Hodges A, Strand AD, Aragaki AK, et al. Regional and cellular gene expression changes in human Huntington's disease brain. Hum Mol Genet 2006; 15: 965-77.
95. [95] Orr AL, Li S, Wang CE, et al. N-terminal mutant huntingtin associates with mitochondria and impairs mitochondrial trafficking. J Neurosci 2008; 28: 2783-92.
96. [96] Solans A, Zambrano A, Rodriguez M, Barrientos A. Cytotoxicity of a mutant huntingtin fragment in yeast involves early alterations in mitochondrial OXPHOS complexes II and III. Hum Mol Genet 2006; 15: 3063-81.
97. [97] 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.
98. [98] Staiger H, Stefan N, Machicao F, Fritsche A, Haring HU. PPARGC1A mRNA levels of in vitro differentiated human skeletal muscle cells are negatively associated with the plasma oleate concentrations of the donors. Diabetologia 2006; 49: 212-4.
99. [99] Liesa M, Borda-d'Agua B, Medina-Gomez G, et al. Mitochondrial fusion is increased by the nuclear coactivator PGC-1beta. PLoS One 2008; 3: e3613.
100. [100] Westermann B. Mitochondrial fusion and fission in cell life and death. Nat Rev Mol Cell Biol 2010; 11: 872-84.
101. [101] Zuchner S, Mersiyanova IV, Muglia M, et al. Mutations in the mitochondrial GTPase mitofusin 2 cause Charcot-Marie-Tooth neuropathy type 2A. Nat Genet 2004; 36: 449-51.
102. [102] Bach D, Naon D, Pich S, et al. Expression of Mfn2, the Charcot-Marie-Tooth neuropathy type 2A gene, in human skeletal muscle: effects of type 2 diabetes, obesity, weight loss, and the regulatory role of tumor necrosis factor alpha and interleukin-6. Diabetes 2005; 54: 2685-93.
103. [103] 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.
104. [104] Patti ME, Butte AJ, Crunkhorn S, et al. Coordinated reduction of genes of oxidative metabolism in humans with insulin resistance and diabetes: Potential role of PGC1 and NRF1. Proc Natl Acad Sci U S A 2003; 100: 8466-71.
105. [105] Win N, Needs M, Rahman S, Gold P, Ward S. An unusual case of an acute hemolytic transfusion reaction caused by an autoanti-I. Immunohematology 2011; 27: 101-3.
106. [106] Sebastian D, Hernandez-Alvarez MI, Segales J, et al. Mitofusin 2 (Mfn2) links mitochondrial and endoplasmic reticulum function with insulin signaling and is essential for normal glucose homeostasis. Proc Natl Acad Sci U S A 2012; 109: 5523-8.
107. [107] Peprah E. Fragile X syndrome: the FMR1 CGG repeat distribution among world populations. Ann Hum Genet 2012; 76: 178-91.
108. [108] Kumari D, Usdin K. Interaction of the transcription factors USF1, USF2, and alpha-Pal/Nrf-1 with the FMR1 promoter. Implications for Fragile X mental retardation syndrome. J Biol Chem 2001; 276: 4357-64.
109. [109] Mahishi L, Usdin K. NF-Y, AP2, Nrf1 and Sp1 regulate the fragile X-related gene 2 (FXR2). Biochem J 2006; 400: 327-35.
110. [110] Hsieh YC, Yang S, Choudhry MA, et al. PGC-1 upregulation via estrogen receptors: a common mechanism of salutary effects of estrogen and flutamide on heart function after trauma-hemorrhage. Am J Physiol Heart Circ Physiol 2005; 289: H2665-72.
111. [111] Mattingly KA, Ivanova MM, Riggs KA, et al. Estradiol stimulates transcription of nuclear respiratory factor-1 and increases mitochondrial biogenesis. Mol Endocrinol 2008; 22: 609-22.
112. [112] Angus LM, Chakkalakal JV, Mejat A, et al. Calcineurin-NFAT signaling, together with GABP and peroxisome PGC-1{alpha}, drives utrophin gene expression at the neuromuscular junction. Am J Physiol Cell Physiol 2005; 289: C908-17.
113. [113] Yoshida Y, Hasegawa J, Nezu R, et al. Clinical usefulness of mitochondrial transcription factor A expression as a predictive marker in colorectal cancer patients treated with FOLFOX. Cancer Sci 2011; 102: 578-82.
114. [114] Santos JM, Tewari S, Goldberg AF, Kowluru RA. Mitochondrial biogenesis and the development of diabetic retinopathy. Free Radic Biol Med 2011; 51: 1849-60.
115. [115] Santos JM, Kowluru RA. Role of mitochondria biogenesis in the metabolic memory associated with the continued progression of diabetic retinopathy and its regulation by lipoic acid. Invest Ophthalmol Vis Sci 2011; 52: 8791-8.
116. [116] Brice A, Durr A, Lucking C. Parkin Type of Juvenile Parkinson Disease. 1993.
117. [117] Bouman L, Schlierf A, Lutz AK, et al. Parkin is transcriptionally regulated by ATF4: evidence for an interconnection between mitochondrial stress and ER stress. Cell Death Differ 2011; 18: 769-82.
118. [118] Kim KY, Sack MN. Parkin in the regulation of fat uptake and mitochondrial biology: emerging links in the pathophysiology of Parkinson's disease. Curr Opin Lipidol 2012; 23: 201-5.
119. [119] Schneider SA, Klein C. PINK1 Type of Young-Onset Parkinson Disease. 1993.
120. [120] Grunewald A, Gegg ME, Taanman JW, et al. Differential effects of PINK1 nonsense and missense mutations on mitochondrial function and morphology. Exp Neurol 2009; 219: 266-73.
121. [121] Kim JA, Wei Y, Sowers JR. Role of mitochondrial dysfunction in insulin resistance. Circ Res 2008; 102: 401-14.
122. [122] Lowell BB, Shulman GI. Mitochondrial dysfunction and type 2 diabetes. Science 2005; 307: 384-7.
123. [123] Garnier A, Fortin D, Delomenie C, et al. Depressed mitochondrial transcription factors and oxidative capacity in rat failing cardiac and skeletal muscles. J Physiol 2003; 551: 491-501.
124. [124] Garnier A, Zoll J, Fortin D, et al. Control by circulating factors of mitochondrial function and transcription cascade in heart failure: a role for endothelin-1 and angiotensin II. Circ Heart Fail 2009; 2: 342-50.
125. [125] Arany Z, He H, Lin J, et al. Transcriptional coactivator PGC-1 alpha controls the energy state and contractile function of cardiac muscle. Cell Metab 2005; 1: 259-71.
126. [126] Huss JM, Kopp RP, Kelly DP. Peroxisome proliferator-activated receptor coactivator-1alpha (PGC-1alpha) coactivates the cardiacenriched nuclear receptors estrogen-related receptor-alpha and-gamma. Identification of novel leucine-rich interaction motif within PGC-1alpha. J Biol Chem 2002; 277: 40265-74.
127. [127] Lehman JJ, Barger PM, Kovacs A, et al. Peroxisome proliferatoractivated receptor gamma coactivator-1 promotes cardiac mitochondrial biogenesis. J Clin Invest 2000; 106: 847-56.
128. [128] Russell LK, Mansfield CM, Lehman JJ, et al. Cardiac-specific induction of the transcriptional coactivator peroxisome proliferatoractivated receptor gamma coactivator-1alpha promotes mitochondrial biogenesis and reversible cardiomyopathy in a developmental stage-dependent manner. Circ Res 2004; 94: 525-33.
129. [129] Rimbaud S, Garnier A, Ventura-Clapier R. Mitochondrial biogenesis in cardiac pathophysiology. Pharmacol Rep 2009; 61: 131-8.
130. [130] Kemi OJ, Hoydal MA, Haram PM, et al. Exercise training restores aerobic capacity and energy transfer systems in heart failure treated with losartan. Cardiovasc Res 2007; 76: 91-9.
131. [131] Sun CK, Chang LT, Sheu JJ, et al. Losartan preserves integrity of cardiac gap junctions and PGC-1 alpha gene expression and prevents cellular apoptosis in remote area of left ventricular myocardium following acute myocardial infarction. Int Heart J 2007; 48: 533-46.
132. [132] Witt H, Schubert C, Jaekel J, et al. Sex-specific pathways in early cardiac response to pressure overload in mice. J Mol Med (Berl) 2008; 86: 1013-24.
133. [133] Sebastiani M, Giordano C, Nediani C, et al. Induction of mitochondrial biogenesis is a maladaptive mechanism in mitochondrial cardiomyopathies. J Am Coll Cardiol 2007; 50: 1362-9.
134. [134] Javadov S, Huang C, Kirshenbaum L, Karmazyn M. NHE-1 inhibition improves impaired mitochondrial permeability transition and respiratory function during postinfarction remodelling in the rat. J Mol Cell Cardiol 2005; 38: 135-43.
135. [135] Jullig M, Hickey AJ, Chai CC, et al. Is the failing heart out of fuel or a worn engine running rich? A study of mitochondria in old spontaneously hypertensive rats. Proteomics 2008; 8: 2556-72.
136. [136] Arany Z, Novikov M, Chin S, et al. Transverse aortic constriction leads to accelerated heart failure in mice lacking PPAR-gamma coactivator 1alpha. Proc Natl Acad Sci U S A 2006; 103: 10086-91.
137. [137] Sack MN, Rader TA, Park S, et al. Fatty acid oxidation enzyme gene expression is downregulated in the failing heart. Circulation 1996; 94: 2837-42.
138. [138] Lehman JJ, Kelly DP. Transcriptional activation of energy metabolic switches in the developing and hypertrophied heart. Clin Exp Pharmacol Physiol 2002; 29: 339-45.
139. [139] Nisoli E, Clementi E, Carruba MO, Moncada S. Defective mitochondrial biogenesis: a hallmark of the high cardiovascular risk in the metabolic syndrome? Circ Res 2007; 100: 795-806.
140. [140] Wang S, Fu C, Wang H, et al. Polymorphisms of the peroxisome proliferator-activated receptor-gamma coactivator-1alpha gene are associated with hypertrophic cardiomyopathy and not with hypertension hypertrophy. Clin Chem Lab Med 2007; 45: 962-7.
141. [141] Haq S, Choukroun G, Lim H, et al. Differential activation of signal transduction pathways in human hearts with hypertrophy versus advanced heart failure. Circulation 2001; 103: 670-7.
142. [142] Tian R, Musi N, D'Agostino J, Hirshman MF, Goodyear LJ. Increased adenosine monophosphate-activated protein kinase activity in rat hearts with pressure-overload hypertrophy. Circulation 2001; 104: 1664-9.
143. [143] Russell RR, III, Li J, Coven DL, et al. AMP-activated protein kinase mediates ischemic glucose uptake and prevents postischemic cardiac dysfunction, apoptosis, and injury. J Clin Invest 2004; 114: 495-503.
144. [144] Kinugawa K, Yonekura K, Ribeiro RC, et al. Regulation of thyroid hormone receptor isoforms in physiological and pathological cardiac hypertrophy. Circ Res 2001; 89: 591-8.
145. [145] Wassen FW, Schiel AE, Kuiper GG, et al. Induction of thyroid hormone-degrading deiodinase in cardiac hypertrophy and failure. Endocrinology 2002; 143: 2812-5.
146. [146] Cook SA, Matsui T, Li L, Rosenzweig A. Transcriptional effects of chronic Akt activation in the heart. J Biol Chem 2002; 277: 22528-33.
147. [147] Nishio Y, Kanazawa A, Nagai Y, Inagaki H, Kashiwagi A. Regulation and role of the mitochondrial transcription factor in the diabetic rat heart. Ann N Y Acad Sci 2004; 1011: 78-85.
148. [148] Chang LT, Sun CK, Wang CY, et al. Downregulation of peroxisme proliferator activated receptor gamma co-activator 1alpha in diabetic rats. Int Heart J 2006; 47: 901-10.
149. [149] Reznick RM, Zong H, Li J, et al. Aging-associated reductions in AMP-activated protein kinase activity and mitochondrial biogenesis. Cell Metab 2007; 5: 151-6.
150. [150] Wu Z, Puigserver P, Andersson U, et al. Mechanisms controlling mitochondrial biogenesis and respiration through the thermogenic coactivator PGC-1. Cell 1999; 98: 115-24.
151. [151] Semple RK, Crowley VC, Sewter CP, et al. Expression of the thermogenic nuclear hormone receptor coactivator PGC-1alpha is reduced in the adipose tissue of morbidly obese subjects. Int J Obes Relat Metab Disord 2004; 28: 176-9.
152. [152] Roden M. Muscle triglycerides and mitochondrial function: possible mechanisms for the development of type 2 diabetes. Int J Obes (Lond) 2005; 29 Suppl 2: S111-5.
153. [153] Hoeks J, Hesselink MK, Russell AP, et al. Peroxisome proliferatoractivated receptor-gamma coactivator-1 and insulin resistance: acute effect of fatty acids. Diabetologia 2006; 49: 2419-26.
154. [154] Kelley DE, He J, Menshikova EV, Ritov VB. Dysfunction of mitochondria in human skeletal muscle in type 2 diabetes. Diabetes 2002; 51: 2944-50.
155. [155] Petersen KF, Dufour S, Befroy D, Garcia R, Shulman GI. Impaired mitochondrial activity in the insulin-resistant offspring of patients with type 2 diabetes. N Engl J Med 2004; 350: 664-71.
156. [156] Russell AP. PGC-1alpha and exercise: important partners in combating insulin resistance. Curr Diabetes Rev 2005; 1: 175-81.
157. [157] Benton CR, Wright DC, Bonen A. PGC-1alpha-mediated regulation of gene expression and metabolism: implications for nutrition and exercise prescriptions. Appl Physiol Nutr Metab 2008; 33: 843-62.
158. [158] Earnest CP. Exercise interval training: an improved stimulus for improving the physiology of pre-diabetes. Med Hypotheses 2008; 71: 752-61.
159. [159] Bergeron R, Russell RR, III, Young LH, et al. Effect of AMPK activation on muscle glucose metabolism in conscious rats. Am J Physiol 1999; 276: E938-44.
160. [160] Hayashi T, Hirshman MF, Kurth EJ, Winder WW, Goodyear LJ. Evidence for 5' AMP-activated protein kinase mediation of the effect of muscle contraction on glucose transport. Diabetes 1998; 47: 1369-73.
161. [161] Merrill GF, Kurth EJ, Hardie DG, Winder WW. AICA riboside increases AMP-activated protein kinase, fatty acid oxidation, and glucose uptake in rat muscle. Am J Physiol 1997; 273: E1107-12.
162. [162] Russell RR, III, Bergeron R, Shulman GI, Young LH. Translocation of myocardial GLUT-4 and increased glucose uptake through activation of AMPK by AICAR. Am J Physiol 1999; 277: H643-9.
163. [163] Ruderman NB, Cacicedo JM, Itani S, et al. Malonyl-CoA and AMP-activated protein kinase (AMPK): possible links between insulin resistance in muscle and early endothelial cell damage in diabetes. Biochem Soc Trans 2003; 31: 202-6.
164. [164] Isomaa B, Almgren P, Tuomi T, et al. Cardiovascular morbidity and mortality associated with the metabolic syndrome. Diabetes Care 2001; 24: 683-9.
165. [165] Trevisan M, Liu J, Bahsas FB, Menotti A. Syndrome X and mortality: a population-based study. Risk Factor and Life Expectancy Research Group. Am J Epidemiol 1998; 148: 958-66.
166. [166] Guarente L. Sirtuins as potential targets for metabolic syndrome. Nature 2006; 444: 868-74.
167. [167] Zhang BB, Zhou G, Li C. AMPK: an emerging drug target for diabetes and the metabolic syndrome. Cell Metab 2009; 9: 407-16.
168. [168] Chaudhary N, Pfluger PT. Metabolic benefits from Sirt1 and Sirt1 activators. Curr Opin Clin Nutr Metab Care 2009; 12: 431-7.
169. [169] Pfluger PT, Herranz D, Velasco-Miguel S, Serrano M, Tschop MH. Sirt1 protects against high-fat diet-induced metabolic damage. Proc Natl Acad Sci U S A 2008; 105: 9793-8.
170. [170] Liang F, Kume S, Koya D. SIRT1 and insulin resistance. Nat Rev Endocrinol 2009; 5: 367-73.
171. [171] Andersson U, Scarpulla RC. Pgc-1-related coactivator, a novel, serum-inducible coactivator of nuclear respiratory factor 1-dependent transcription in mammalian cells. Mol Cell Biol 2001; 21: 3738-49.
172. [172] Weinberg JM. Mitochondrial biogenesis in kidney disease. J Am Soc Nephrol 2011; 22: 431-6.
173. [173] Funk JA, Odejinmi S, Schnellmann RG. SRT1720 induces mitochondrial biogenesis and rescues mitochondrial function after oxidant injury in renal proximal tubule cells. J Pharmacol Exp Ther 2010; 333: 593-601.
174. [174] Rasbach KA, Funk JA, Jayavelu T, Green PT, Schnellmann RG. 5-hydroxytryptamine receptor stimulation of mitochondrial biogenesis. J Pharmacol Exp Ther 2010; 332: 632-9.
175. [175] Rasbach KA, Schnellmann RG. Signaling of mitochondrial biogenesis following oxidant injury. J Biol Chem 2007; 282: 2355-62.
176. [176] Rasbach KA, Schnellmann RG. PGC-1alpha over-expression promotes recovery from mitochondrial dysfunction and cell injury. Biochem Biophys Res Commun 2007; 355: 734-9.
177. [177] Rasbach KA, Schnellmann RG. Isoflavones promote mitochondrial biogenesis. J Pharmacol Exp Ther 2008; 325: 536-43.
178. [178] Borniquel S, Valle I, Cadenas S, Lamas S, Monsalve M. Nitric oxide regulates mitochondrial oxidative stress protection via the transcriptional coactivator PGC-1alpha. FASEB J 2006; 20: 1889-91.
179. [179] Quaggin SE, Coffman TM. Toward a mouse model of diabetic nephropathy: is endothelial nitric oxide synthase the missing link? J Am Soc Nephrol 2007; 18: 364-6.
180. [180] Brosius FC, III, Alpers CE, Bottinger EP, et al. Mouse models of diabetic nephropathy. J Am Soc Nephrol 2009; 20: 2503-12.
181. [181] Ventura-Clapier R, Garnier A, Veksler V. Transcriptional control of mitochondrial biogenesis: the central role of PGC-1alpha. Cardiovasc Res 2008; 79: 208-17.
182. [182] Ruan X, Zheng F, Guan Y. PPARs and the kidney in metabolic syndrome. Am J Physiol Renal Physiol 2008; 294: F1032-47.
183. [183] Wang XX, Jiang T, Levi M. Nuclear hormone receptors in diabetic nephropathy. Nat Rev Nephrol 2010; 6: 342-51.
184. [184] Hondares E, Pineda-Torra I, Iglesias R, et al. PPARdelta, but not PPARalpha, activates PGC-1alpha gene transcription in muscle. Biochem Biophys Res Commun 2007; 354: 1021-7.
185. [185] Kamijo Y, Hora K, Kono K, et al. PPARalpha protects proximal tubular cells from acute fatty acid toxicity. J Am Soc Nephrol 2007; 18: 3089-100.
186. [186] Li S, Wu P, Yarlagadda P, et al. PPAR alpha ligand protects during cisplatin-induced acute renal failure by preventing inhibition of renal FAO and PDC activity. Am J Physiol Renal Physiol 2004; 286: F572-80.
187. [187] Portilla D, Dai G, McClure T, et al. Alterations of PPARalpha and its coactivator PGC-1 in cisplatin-induced acute renal failure. Kidney Int 2002; 62: 1208-18.
188. [188] Portilla D, Dai G, Peters JM, et al. Etomoxir-induced PPARalphamodulated enzymes protect during acute renal failure. Am J Physiol Renal Physiol 2000; 278: F667-75.
189. [189] Portilla D, Li S, Nagothu KK, et al. Metabolomic study of cisplatin-induced nephrotoxicity. Kidney Int 2006; 69: 2194-204.
190. [190] Nagothu KK, Bhatt R, Kaushal GP, Portilla D. Fibrate prevents cisplatin-induced proximal tubule cell death. Kidney Int 2005; 68: 2680-93.
191. [191] Tracz MJ, Alam J, Nath KA. Physiology and pathophysiology of heme: implications for kidney disease. J Am Soc Nephrol 2007; 18: 414-20.
192. [192] Hasegawa K, Wakino S, Yoshioka K, et al. Kidney-specific overexpression of Sirt1 protects against acute kidney injury by retaining peroxisome function. J Biol Chem 2010; 285: 13045-56.
193. [193] Kume S, Uzu T, Horiike K, et al. Calorie restriction enhances cell adaptation to hypoxia through Sirt1-dependent mitochondrial autophagy in mouse aged kidney. J Clin Invest 2010; 120: 1043-55.
194. [194] He W, Wang Y, Zhang MZ, et al. Sirt1 activation protects the mouse renal medulla from oxidative injury. J Clin Invest 2010; 120: 1056-68.
195. [195] Harman D. Aging: a theory based on free radical and ratiation chemistry. J. Gerontol 1956; 11: 298-300.
196. [196] Miquel J, Economos AC, Fleming J, Johnson JE, Jr. Mitochondrial role in cell aging. Exp Gerontol 1980; 15: 575-91.
197. [197] Rockstein M, Chesky J, Philpott DE, et al. An electron microscopic investigation of age-dependent changes in the flight muscle of Musca domestica L. Gerontologia 1975; 21: 216-23.
198. [198] Sastre J, Pallardo FV, Pla R, et al. Aging of the liver: ageassociated mitochondrial damage in intact hepatocytes. Hepatology 1996; 24: 1199-205.
199. [199] Balagopal P, Schimke JC, Ades P, Adey D, Nair KS. Age effect on transcript levels and synthesis rate of muscle MHC and response to resistance exercise. Am J Physiol Endocrinol Metab 2001; 280: E203-8.
200. [200] Doherty TJ. Invited review: Aging and sarcopenia. J Appl Physiol 2003; 95: 1717-27.
201. [201] Trifunovic A. Mitochondrial DNA and ageing. Biochim Biophys Acta 2006; 1757: 611-7.
202. [202] Vina J, Gomez-Cabrera MC, Borras C, et al. Mitochondrial biogenesis in exercise and in ageing. Adv Drug Deliv Rev 2009; 61: 1369-74.
203. [203] Sandri M, Lin J, Handschin C, et al. PGC-1alpha protects skeletal muscle from atrophy by suppressing FoxO3 action and atrophyspecific gene transcription. Proc Natl Acad Sci U S A 2006; 103: 16260-5.
204. [204] Derbre F, Gomez-Cabrera MC, Nascimento AL, et al. Age associated low mitochondrial biogenesis may be explained by lack of response of PGC-1alpha to exercise training. Age (Dordr) 2011.
205. [205] Williamson D, Gallagher P, Harber M, Hollon C, Trappe S. Mitogen-activated protein kinase (MAPK) pathway activation: effects of age and acute exercise on human skeletal muscle. J Physiol 2003; 547: 977-87.
206. [206] Goldspink DF, Morton AJ, Loughna P, Goldspink G. The effect of hypokinesia and hypodynamia on protein turnover and the growth of four skeletal muscles of the rat. Pflugers Arch 1986; 407: 333-40.
207. [207] Marzani B, Balage M, Venien A, et al. Antioxidant supplementation restores defective leucine stimulation of protein synthesis in skeletal muscle from old rats. J Nutr 2008; 138: 2205-11.
208. [208] Spangenburg EE. Changes in muscle mass with mechanical load: possible cellular mechanisms. Appl Physiol Nutr Metab 2009; 34: 328-35.
209. [209] Wu M, Liu H, Fannin J, et al. Acetaminophen improves protein translational signaling in aged skeletal muscle. Rejuvenation Res 2010; 13: 571-9.
210. [210] Sanchis-Gomar F. Sestrins: Novel antioxidant and AMPKmodulating functions regulated by exercise? J Cell Physiol 2013.
211. [211] Garcia-Gimenez JL, Sanchis-Gomar F, Pallardo FV. Could thiazolidinediones increase the risk of heart failure in Friedreich's ataxia patients? Mov Disord 2011; 26: 769-71.
212. [212] Marmolino D, Acquaviva F, Pinelli M, et al. PPAR-gamma agonist Azelaoyl PAF increases frataxin protein and mRNA expression: new implications for the Friedreich's ataxia therapy. Cerebellum 2009; 8: 98-103.
213. [213] Handschin C. The biology of PGC-1alpha and its therapeutic potential. Trends Pharmacol Sci 2009; 30: 322-9.
214. [214] 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.
215. [215] Viscomi C, Bottani E, Civiletto G, et al. In vivo correction of COX deficiency by activation of the AMPK/PGC-1alpha axis. Cell Metab 2011; 14: 80-90.
216. [216] Yatsuga S, Suomalainen A. Effect of bezafibrate treatment on lateonset mitochondrial myopathy in mice. Hum Mol Genet 2012; 21: 526-35.
217. [217] Piao Y, Kim HG, Oh MS, Pak YK. Overexpression of TFAM, NRF-1 and myr-AKT protects the MPP(+)-induced mitochondrial dysfunctions in neuronal cells. Biochim Biophys Acta 2012; 1820: 577-85.
218. [218] Klinkenberg M, Gispert S, Dominguez-Bautista JA, et al. Restriction of trophic factors and nutrients induces PARKIN expression. Neurogenetics 2012; 13: 9-21.
219. [219] Fitzgerald JC, Plun-Favreau H. Emerging pathways in genetic Parkinson's disease: autosomal-recessive genes in Parkinson's disease--a common pathway? FEBS J 2008; 275: 5758-66.
220. [220] Colca JR. Insulin sensitizers may prevent metabolic inflammation. Biochem Pharmacol 2006; 72: 125-31.
221. [221] Wilson-Fritch L, Burkart A, Bell G, et al. Mitochondrial biogenesis and remodeling during adipogenesis and in response to the insulin sensitizer rosiglitazone. Mol Cell Biol 2003; 23: 1085-94.
222. [222] Wilson-Fritch L, Nicoloro S, Chouinard M, et al. Mitochondrial remodeling in adipose tissue associated with obesity and treatment with rosiglitazone. J Clin Invest 2004; 114: 1281-9.
223. [223] Bogacka I, Xie H, Bray GA, Smith SR. Pioglitazone induces mitochondrial biogenesis in human subcutaneous adipose tissue in vivo. Diabetes 2005; 54: 1392-9.
224. [224] Bogacka I, Ukropcova B, McNeil M, Gimble JM, Smith SR. Structural and functional consequences of mitochondrial biogenesis in human adipocytes in vitro. J Clin Endocrinol Metab 2005; 90: 6650-6.
225. [225] Kukidome D, Nishikawa T, Sonoda K, et al. Activation of AMPactivated protein kinase reduces hyperglycemia-induced mitochondrial reactive oxygen species production and promotes mitochondrial biogenesis in human umbilical vein endothelial cells. Diabetes 2006; 55: 120-7.
226. [226] Suwa M, Egashira T, Nakano H, Sasaki H, Kumagai S. Metformin increases the PGC-1alpha protein and oxidative enzyme activities possibly via AMPK phosphorylation in skeletal muscle in vivo. J Appl Physiol 2006; 101: 1685-92.
227. [227] Civitarese AE, Ukropcova B, Carling S, et al. Role of adiponectin in human skeletal muscle bioenergetics. Cell Metab 2006; 4: 75-87.
228. [228] Konstantinopoulos PA, Karamouzis MV, Papavassiliou AG. Effect of aspirin use on thiazolidinediones and cardiovascular events. JAMA 2008; 299: 1539; author reply 1539-40.
229. [229] 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.
230. [230] Kume S, Uzu T, Kashiwagi A, Koya D. SIRT1, a calorie restriction mimetic, in a new therapeutic approach for type 2 diabetes mellitus and diabetic vascular complications. Endocr Metab Immune Disord Drug Targets 2010; 10: 16-24.
231. [231] Park SJ, Ahmad F, Philp A, et al. Resveratrol ameliorates agingrelated metabolic phenotypes by inhibiting cAMP phosphodiesterases. Cell 2012; 148: 421-33.
232. [232] Palacios OM, Carmona JJ, Michan S, et al. Diet and exercise signals regulate SIRT3 and activate AMPK and PGC-1alpha in skeletal muscle. Aging (Albany NY) 2009; 1: 771-83.
233. [233] Ojuka EO, Nolte LA, Holloszy JO. Increased expression of GLUT-4 and hexokinase in rat epitrochlearis muscles exposed to AICAR in vitro. J Appl Physiol 2000; 88: 1072-5.
234. [234] Bergeron R, Ren JM, Cadman KS, et al. Chronic activation of AMP kinase results in NRF-1 activation and mitochondrial biogenesis. Am J Physiol Endocrinol Metab 2001; 281: E1340-6.
235. [235] Zong H, Ren JM, Young LH, et al. AMP kinase is required for mitochondrial biogenesis in skeletal muscle in response to chronic energy deprivation. Proc Natl Acad Sci U S A 2002; 99: 15983-7.
236. [236] Shi Y, Hon M, Evans RM. The peroxisome proliferator-activated receptor delta, an integrator of transcriptional repression and nuclear receptor signaling. Proc Natl Acad Sci U S A 2002; 99: 2613-8.
237. [237] Winder WW, Holmes BF, Rubink DS, et al. Activation of AMPactivated protein kinase increases mitochondrial enzymes in skeletal muscle. J Appl Physiol 2000; 88: 2219-26.
238. [238] Handschin C, Chin S, Li P, et al. Skeletal muscle fiber-type switching, exercise intolerance, and myopathy in PGC-1alpha musclespecific knock-out animals. J Biol Chem 2007; 282: 30014-21.
239. [239] Sanchis-Gomar F, Lippi G, Mayero S, Perez-Quilis C, Garcia-Gimenez JL. Irisin: a new potential hormonal target for the treatment of obesity and type 2 diabetes. J Diabetes 2012; 4: 196.
240. [240] Burks TN, Andres-Mateos E, Marx R, et al. Losartan restores skeletal muscle remodeling and protects against disuse atrophy in sarcopenia. Sci Transl Med 2011; 3: 82-37.
241. [241] Feng X, Luo Z, Ma L, et al. Angiotensin II receptor blocker telmisartan enhances running endurance of skeletal muscle through activation of the PPAR delta/ AMPK pathway. J Cell Mol Med 2010.
242. [242] He H, Yang D, Ma L, et al. Telmisartan prevents weight gain and obesity through activation of peroxisome proliferator-activated receptor-delta-dependent pathways. Hypertension 2010; 55: 869-79.
243. [243] Sanchis-Gomar F, Gomez-Cabrera MC, Vina J. The loss of muscle mass and sarcopenia: non hormonal intervention. Exp Gerontol 2011; 46: 967-9.
244. [244] Sanchis-Gomar F, Lippi G. Telmisartan as metabolic modulator: a new perspective in sports doping? J Strength Cond Res 2012; 26: 608-10.