New insights into PGC-1 coactivators: Redefining their role in the regulation of mitochondrial function and beyond

FEBS Journal

Volumn 282, Issue 4, 2015, Pages 647-672

  Villena, Josep A ^a,b  

^a UNIVERSITAT AUTÒNOMA DE BARCELONA   (Spain)

^b INSTITUTO DE SALUD CARLOS III   (Spain)

Author keywords

energy metabolism; metabolic disease; mitochondrial biogenesis; OxPhos; PGC 1 ; PGC 1 ; PRC; transcriptional regulation

Indexed keywords

PEROXISOME PROLIFERATOR ACTIVATED RECEPTOR GAMMA COACTIVATOR 1 RELATED COACTIVATOR; PEROXISOME PROLIFERATOR ACTIVATED RECEPTOR GAMMA COACTIVATOR 1ALPHA; PEROXISOME PROLIFERATOR ACTIVATED RECEPTOR GAMMA COACTIVATOR 1BETA; TRANSCRIPTION FACTOR; UNCLASSIFIED DRUG; PEROXISOME-PROLIFERATOR-ACTIVATED RECEPTOR-GAMMA COACTIVATOR-1;

ALZHEIMER DISEASE; BIOGENESIS; BLOOD CELL; BROWN ADIPOSE TISSUE; CELL FUNCTION; CELLULAR STRESS SIGNAL; DISORDERS OF MITOCHONDRIAL FUNCTIONS; GENE; GENE EXPRESSION; HEART DISEASE; HEART FUNCTION; HOMEOSTASIS; HUMAN; HUNTINGTON CHOREA; LIVER METABOLISM; MALIGNANT NEOPLASTIC DISEASE; MITOCHONDRIAL DYNAMICS; MUSCULAR DYSTROPHY; MYOPATHY; NERVOUS TISSUE; NON INSULIN DEPENDENT DIABETES MELLITUS; NONHUMAN; PARKINSON DISEASE; PATHOGENESIS; PGC 1ALPHA GENE; PGC 1BETA GENE; PRIORITY JOURNAL; PROTEIN FUNCTION; PROTEIN STRUCTURE; REGULATORY MECHANISM; REVIEW; SKELETAL MUSCLE; WHITE ADIPOSE TISSUE; ANIMAL; ENERGY METABOLISM; GENETICS; METABOLISM; MITOCHONDRION; MOUSE; PHYSIOLOGY;

ANIMALS; ENERGY METABOLISM; HUMANS; MICE; MITOCHONDRIA; MITOCHONDRIAL TURNOVER; TRANSCRIPTION FACTORS;

EID: 84923138740     PISSN: 1742464X     EISSN: 17424658     Source Type: Journal    
DOI: 10.1111/febs.13175     Document Type: Review

References (167)

1. Puigserver P, Adelmant G, Wu Z, Fan M, Xu J, O'Malley B, &, Spiegelman BM, (1999) Activation of PPARgamma coactivator-1 through transcription factor docking. Science 286, 1368-1371.
2. Kressler D, Schreiber SN, Knutti D, &, Kralli A, (2002) The PGC-1-related protein PERC is a selective coactivator of estrogen receptor alpha. J Biol Chem 277, 13918-13925.
3. Lin J, Puigserver P, Donovan J, Tarr P, &, Spiegelman BM, (2002) Peroxisome proliferator-activated receptor gamma coactivator 1beta (PGC-1beta), a novel PGC-1-related transcription coactivator associated with host cell factor. J Biol Chem 277, 1645-1648.
4. Monsalve M, Wu Z, Adelmant G, Puigserver P, Fan M, &, Spiegelman BM, (2000) Direct coupling of transcription and mRNA processing through the thermogenic coactivator PGC-1. Mol Cell 6, 307-316.
5. Chang JS, Fernand V, Zhang Y, Shin J, Jun HJ, Joshi Y, &, Gettys TW, (2012) NT-PGC-1alpha protein is sufficient to link beta3-adrenergic receptor activation to transcriptional and physiological components of adaptive thermogenesis. J Biol Chem 287, 9100-9111.
6. Zhang Y, Huypens P, Adamson AW, Chang JS, Henagan TM, Boudreau A, Lenard NR, Burk D, Klein J, Perwitz N, et al,. (2009) Alternative mRNA splicing produces a novel biologically active short isoform of PGC-1alpha. J Biol Chem 284, 32813-32826.
7. Ruas JL, White JP, Rao RR, Kleiner S, Brannan KT, Harrison BC, Greene NP, Wu J, Estall JL, Irving BA, et al,. (2012) A PGC-1alpha isoform induced by resistance training regulates skeletal muscle hypertrophy. Cell 151, 1319-1331.
8. Cunningham JT, Rodgers JT, Arlow DH, Vazquez F, Mootha VK, &, Puigserver P, (2007) mTOR controls mitochondrial oxidative function through a YY1-PGC-1alpha transcriptional complex. Nature 450, 736-740.
9. Michael LF, Wu Z, Cheatham RB, Puigserver P, Adelmant G, Lehman JJ, Kelly DP, &, Spiegelman BM, (2001) Restoration of insulin-sensitive glucose transporter (GLUT4) gene expression in muscle cells by the transcriptional coactivator PGC-1. Proc Natl Acad Sci USA 98, 3820-3825.
10. Puigserver P, Rhee J, Donovan J, Walkey CJ, Yoon JC, Oriente F, Kitamura Y, Altomonte J, Dong H, Accili D, et al,. (2003) Insulin-regulated hepatic gluconeogenesis through FOXO1-PGC-1alpha interaction. Nature 423, 550-555.
11. Puigserver P, Wu Z, Park CW, Graves R, Wright M, &, Spiegelman BM, (1998) A cold-inducible coactivator of nuclear receptors linked to adaptive thermogenesis. Cell 92, 829-839.
12. Li S, Liu C, Li N, Hao T, Han T, Hill DE, Vidal M, &, Lin JD, (2008) Genome-wide coactivation analysis of PGC-1alpha identifies BAF60a as a regulator of hepatic lipid metabolism. Cell Metab 8, 105-117.
13. Wallberg AE, Yamamura S, Malik S, Spiegelman BM, &, Roeder RG, (2003) Coordination of p300-mediated chromatin remodeling and TRAP/mediator function through coactivator PGC-1alpha. Mol Cell 12, 1137-1149.
14. Leone TC, Lehman JJ, Finck BN, Schaeffer PJ, Wende AR, Boudina S, Courtois M, Wozniak DF, Sambandam N, Bernal-Mizrachi C, et al,. (2005) PGC-1alpha deficiency causes multi-system energy metabolic derangements: muscle dysfunction, abnormal weight control and hepatic steatosis. PLoS Biol 3, e101.
15. Lin J, Wu PH, Tarr PT, Lindenberg KS, St-Pierre J, Zhang CY, Mootha VK, Jager S, Vianna CR, Reznick RM, et al,. (2004) Defects in adaptive energy metabolism with CNS-linked hyperactivity in PGC-1alpha null mice. Cell 119, 121-135.
16. Yoon JC, Puigserver P, Chen G, Donovan J, Wu Z, Rhee J, Adelmant G, Stafford J, Kahn CR, Granner DK, et al,. (2001) Control of hepatic gluconeogenesis through the transcriptional coactivator PGC-1. Nature 413, 131-138.
17. Andersson U, &, Scarpulla RC, (2001) Pgc-1-related coactivator, a novel, serum-inducible coactivator of nuclear respiratory factor 1-dependent transcription in mammalian cells. Mol Cell Biol 21, 3738-3749.
18. Fan M, Rhee J, St-Pierre J, Handschin C, Puigserver P, Lin J, Jaeger S, Erdjument-Bromage H, Tempst P, &, Spiegelman BM, (2004) Suppression of mitochondrial respiration through recruitment of p160 myb binding protein to PGC-1alpha: modulation by p38 MAPK. Genes Dev 18, 278-289.
19. Knutti D, Kressler D, &, Kralli A, (2001) Regulation of the transcriptional coactivator PGC-1 via MAPK-sensitive interaction with a repressor. Proc Natl Acad Sci USA 98, 9713-9718.
20. Puigserver P, Rhee J, Lin J, Wu Z, Yoon JC, Zhang CY, Krauss S, Mootha VK, Lowell BB, &, Spiegelman BM, (2001) Cytokine stimulation of energy expenditure through p38 MAP kinase activation of PPARgamma coactivator-1. Mol Cell 8, 971-982.
21. Li X, Monks B, Ge Q, &, Birnbaum MJ, (2007) Akt/PKB regulates hepatic metabolism by directly inhibiting PGC-1alpha transcription coactivator. Nature 447, 1012-1016.
22. Lustig Y, Ruas JL, Estall JL, Lo JC, Devarakonda S, Laznik D, Choi JH, Ono H, Olsen JV, &, Spiegelman BM, (2011) Separation of the gluconeogenic and mitochondrial functions of PGC-1{alpha} through S6 kinase. Genes Dev 25, 1232-1244.
23. Jager S, Handschin C, St-Pierre J, &, Spiegelman BM, (2007) AMP-activated protein kinase (AMPK) action in skeletal muscle via direct phosphorylation of PGC-1alpha. Proc Natl Acad Sci USA 104, 12017-12022.
24. Olson BL, Hock MB, Ekholm-Reed S, Wohlschlegel JA, Dev KK, Kralli A, &, Reed SI, (2008) SCFCdc4 acts antagonistically to the PGC-1alpha transcriptional coactivator by targeting it for ubiquitin-mediated proteolysis. Genes Dev 22, 252-264.
25. Teyssier C, Ma H, Emter R, Kralli A, &, Stallcup MR, (2005) Activation of nuclear receptor coactivator PGC-1alpha by arginine methylation. Genes Dev 19, 1466-1473.
26. Lerin C, Rodgers JT, Kalume DE, Kim SH, Pandey A, &, Puigserver P, (2006) GCN5 acetyltransferase complex controls glucose metabolism through transcriptional repression of PGC-1alpha. Cell Metab 3, 429-438.
27. Gerhart-Hines Z, Rodgers JT, Bare O, Lerin C, Kim SH, Mostoslavsky R, Alt FW, Wu Z, &, Puigserver P, (2007) Metabolic control of muscle mitochondrial function and fatty acid oxidation through SIRT1/PGC-1alpha. EMBO J 26, 1913-1923.
28. Rodgers JT, Lerin C, Haas W, Gygi SP, Spiegelman BM, &, Puigserver P, (2005) Nutrient control of glucose homeostasis through a complex of PGC-1alpha and SIRT1. Nature 434, 113-118.
29. Kelly TJ, Lerin C, Haas W, Gygi SP, &, Puigserver P, (2009) GCN5-mediated transcriptional control of the metabolic coactivator PGC-1beta through lysine acetylation. J Biol Chem 284, 19945-19952.
30. Trausch-Azar J, Leone TC, Kelly DP, &, Schwartz AL, (2010) Ubiquitin proteasome-dependent degradation of the transcriptional coactivator PGC-1{alpha} via the N-terminal pathway. J Biol Chem 285, 40192-40200.
31. Chang JS, Huypens P, Zhang Y, Black C, Kralli A, &, Gettys TW, (2010) Regulation of NT-PGC-1alpha subcellular localization and function by protein kinase A-dependent modulation of nuclear export by CRM1. J Biol Chem 285, 18039-18050.
32. Aquilano K, Vigilanza P, Baldelli S, Pagliei B, Rotilio G, &, Ciriolo MR, (2010) 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 285, 21590-21599.
33. Safdar A, Little JP, Stokl AJ, Hettinga BP, Akhtar M, &, Tarnopolsky MA, (2011) Exercise increases mitochondrial PGC-1alpha content and promotes nuclear-mitochondrial cross-talk to coordinate mitochondrial biogenesis. J Biol Chem 286, 10605-10617.
34. Gleyzer N, &, Scarpulla RC, (2011) PGC-1-related coactivator (PRC), a sensor of metabolic stress, orchestrates a redox-sensitive program of inflammatory gene expression. J Biol Chem 286, 39715-39725.
35. Vercauteren K, Gleyzer N, &, Scarpulla RC, (2009) Short hairpin RNA-mediated silencing of PRC (PGC-1-related coactivator) results in a severe respiratory chain deficiency associated with the proliferation of aberrant mitochondria. J Biol Chem 284, 2307-2319.
36. He X, Sun C, Wang F, Shan A, Guo T, Gu W, Cui B, &, Ning G, (2012) Peri-implantation lethality in mice lacking the PGC-1-related coactivator protein. Dev Dyn 241, 975-983.
37. Baar K, Wende AR, Jones TE, Marison M, Nolte LA, Chen M, Kelly DP, &, Holloszy JO, (2002) Adaptations of skeletal muscle to exercise: rapid increase in the transcriptional coactivator PGC-1. FASEB J 16, 1879-1886.
38. Meirhaeghe A, Crowley V, Lenaghan C, Lelliott C, Green K, Stewart A, Hart K, Schinner S, Sethi JK, Yeo G, et al,. (2003) Characterization of the human, mouse and rat PGC1 beta (peroxisome-proliferator-activated receptor-gamma co-activator 1 beta) gene in vitro and in vivo. Biochem J 373, 155-165.
39. Rowe GC, El-Khoury R, Patten IS, Rustin P, &, Arany Z, (2012) PGC-1alpha is dispensable for exercise-induced mitochondrial biogenesis in skeletal muscle. PLoS One 7, e41817.
40. Russell AP, Hesselink MK, Lo SK, &, Schrauwen P, (2005) Regulation of metabolic transcriptional co-activators and transcription factors with acute exercise. FASEB J 19, 986-988.
41. Philp A, Belew MY, Evans A, Pham D, Sivia I, Chen A, Schenk S, &, Baar K, (2011) The PGC-1alpha-related coactivator promotes mitochondrial and myogenic adaptations in C2C12 myotubes. Am J Physiol Regul Integr Comp Physiol 301, R864-872.
42. Mortensen OH, Plomgaard P, Fischer CP, &, Hansen AK, (1985) Pilegaard H & Pedersen BK (2007), PGC-1beta is downregulated by training in human skeletal muscle: no effect of training twice every second day vs. once daily on expression of the PGC-1 family. J Appl Physiol 103, 1536-1542.
43. Wu Z, Puigserver P, Andersson U, Zhang C, Adelmant G, Mootha V, Troy A, Cinti S, Lowell B, Scarpulla RC, et al,. (1999) Mechanisms controlling mitochondrial biogenesis and respiration through the thermogenic coactivator PGC-1. Cell 98, 115-124.
44. Lin J, Wu H, Tarr PT, Zhang CY, Wu Z, Boss O, Michael LF, Puigserver P, Isotani E, Olson EN, et al,. (2002) Transcriptional co-activator PGC-1 alpha drives the formation of slow-twitch muscle fibres. Nature 418, 797-801.
45. Wenz T, Rossi SG, Rotundo RL, Spiegelman BM, &, Moraes CT, (2009) Increased muscle PGC-1alpha expression protects from sarcopenia and metabolic disease during aging. Proc Natl Acad Sci USA 106, 20405-20410.
46. Handschin C, Chin S, Li P, Liu F, Maratos-Flier E, Lebrasseur NK, Yan Z, &, Spiegelman BM, (2007) Skeletal muscle fiber-type switching, exercise intolerance, and myopathy in PGC-1alpha muscle-specific knock-out animals. J Biol Chem 282, 30014-30021.
47. Arany Z, Foo SY, Ma Y, Ruas JL, Bommi-Reddy A, Girnun G, Cooper M, Laznik D, Chinsomboon J, Rangwala SM, et al,. (2008) HIF-independent regulation of VEGF and angiogenesis by the transcriptional coactivator PGC-1alpha. Nature 451, 1008-1012.
48. Handschin C, Kobayashi YM, Chin S, Seale P, Campbell KP, &, Spiegelman BM, (2007) PGC-1alpha regulates the neuromuscular junction program and ameliorates Duchenne muscular dystrophy. Genes Dev 21, 770-783.
49. Russell AP, Feilchenfeldt J, Schreiber S, Praz M, Crettenand A, Gobelet C, Meier CA, Bell DR, Kralli A, Giacobino JP, et al,. (2003) Endurance training in humans leads to fiber type-specific increases in levels of peroxisome proliferator-activated receptor-gamma coactivator-1 and peroxisome proliferator-activated receptor-alpha in skeletal muscle. Diabetes 52, 2874-2881.
50. Adhihetty PJ, Uguccioni G, Leick L, Hidalgo J, Pilegaard H, &, Hood DA, (2009) The role of PGC-1alpha on mitochondrial function and apoptotic susceptibility in muscle. Am J Physiol Cell Physiol 297, C217-225.
51. Chinsomboon J, Ruas J, Gupta RK, Thom R, Shoag J, Rowe GC, Sawada N, Raghuram S, &, Arany Z, (2009) The transcriptional coactivator PGC-1alpha mediates exercise-induced angiogenesis in skeletal muscle. Proc Natl Acad Sci USA 106, 21401-21406.
52. Leick L, Wojtaszewski JF, Johansen ST, Kiilerich K, Comes G, Hellsten Y, Hidalgo J, &, Pilegaard H, (2008) PGC-1alpha is not mandatory for exercise- and training-induced adaptive gene responses in mouse skeletal muscle. Am J Physiol Endocrinol Metab 294, E463-474.
53. Geng T, Li P, Okutsu M, Yin X, Kwek J, Zhang M, &, Yan Z, (2010) PGC-1alpha plays a functional role in exercise-induced mitochondrial biogenesis and angiogenesis but not fiber-type transformation in mouse skeletal muscle. Am J Physiol Cell Physiol 298, C572-579.
54. Civitarese AE, Carling S, Heilbronn LK, Hulver MH, Ukropcova B, Deutsch WA, Smith SR, &, Ravussin E, (2007) Calorie restriction increases muscle mitochondrial biogenesis in healthy humans. PLoS Med 4, e76.
55. Nisoli E, Tonello C, Cardile A, Cozzi V, Bracale R, Tedesco L, Falcone S, Valerio A, Cantoni O, Clementi E, et al,. (2005) Calorie restriction promotes mitochondrial biogenesis by inducing the expression of eNOS. Science 310, 314-317.
56. Finley LW, Lee J, Souza A, Desquiret-Dumas V, Bullock K, Rowe GC, Procaccio V, Clish CB, Arany Z, &, Haigis MC, (2012) Skeletal muscle transcriptional coactivator PGC-1alpha mediates mitochondrial, but not metabolic, changes during calorie restriction. Proc Natl Acad Sci USA 109, 2931-2936.
57. St-Pierre J, Lin J, Krauss S, Tarr PT, Yang R, Newgard CB, &, Spiegelman BM, (2003) Bioenergetic analysis of peroxisome proliferator-activated receptor gamma coactivators 1alpha and 1beta (PGC-1alpha and PGC-1beta) in muscle cells. J Biol Chem 278, 26597-26603.
58. Arany Z, Lebrasseur N, Morris C, Smith E, Yang W, Ma Y, Chin S, &, Spiegelman BM, (2007) The transcriptional coactivator PGC-1beta drives the formation of oxidative type IIX fibers in skeletal muscle. Cell Metab 5, 35-46.
59. Kamei Y, Ohizumi H, Fujitani Y, Nemoto T, Tanaka T, Takahashi N, Kawada T, Miyoshi M, Ezaki O, &, Kakizuka A, (2003) 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 100, 12378-12383.
60. Lelliott CJ, Medina-Gomez G, Petrovic N, Kis A, Feldmann HM, Bjursell M, Parker N, Curtis K, Campbell M, Hu P, et al,. (2006) Ablation of PGC-1beta results in defective mitochondrial activity, thermogenesis, hepatic function, and cardiac performance. PLoS Biol 4, e369.
61. Sonoda J, Mehl IR, Chong LW, Nofsinger RR, &, Evans RM, (2007) PGC-1beta controls mitochondrial metabolism to modulate circadian activity, adaptive thermogenesis, and hepatic steatosis. Proc Natl Acad Sci USA 104, 5223-5228.
62. Vianna CR, Huntgeburth M, Coppari R, Choi CS, Lin J, Krauss S, Barbatelli G, Tzameli I, Kim YB, Cinti S, et al,. (2006) Hypomorphic mutation of PGC-1beta causes mitochondrial dysfunction and liver insulin resistance. Cell Metab 4, 453-464.
63. Zechner C, Lai L, Zechner JF, Geng T, Yan Z, Rumsey JW, Collia D, Chen Z, Wozniak DF, Leone TC, et al,. (2010) Total skeletal muscle PGC-1 deficiency uncouples mitochondrial derangements from fiber type determination and insulin sensitivity. Cell Metab 12, 633-642.
64. Rowe GC, Patten IS, Zsengeller ZK, El-Khoury R, Okutsu M, Bampoh S, Koulisis N, Farrell C, Hirshman MF, Yan Z, et al,. (2013) Disconnecting mitochondrial content from respiratory chain capacity in PGC-1-deficient skeletal muscle. Cell Rep 3, 1449-1456.
65. Koo SH, Satoh H, Herzig S, Lee CH, Hedrick S, Kulkarni R, Evans RM, Olefsky J, &, Montminy M, (2004) PGC-1 promotes insulin resistance in liver through PPAR-alpha-dependent induction of TRB-3. Nat Med 10, 530-534.
66. Rhee J, Inoue Y, Yoon JC, Puigserver P, Fan M, Gonzalez FJ, &, Spiegelman BM, (2003) Regulation of hepatic fasting response by PPARgamma coactivator-1alpha (PGC-1): requirement for hepatocyte nuclear factor 4alpha in gluconeogenesis. Proc Natl Acad Sci USA 100, 4012-4017.
67. Herzig S, Long F, Jhala US, Hedrick S, Quinn R, Bauer A, Rudolph D, Schutz G, Yoon C, Puigserver P, et al,. (2001) CREB regulates hepatic gluconeogenesis through the coactivator PGC-1. Nature 413, 179-183.
68. Lin J, Tarr PT, Yang R, Rhee J, Puigserver P, Newgard CB, &, Spiegelman BM, (2003) PGC-1beta in the regulation of hepatic glucose and energy metabolism. J Biol Chem 278, 30843-30848.
69. Lin J, Yang R, Tarr PT, Wu PH, Handschin C, Li S, Yang W, Pei L, Uldry M, Tontonoz P, et al,. (2005) Hyperlipidemic effects of dietary saturated fats mediated through PGC-1beta coactivation of SREBP. Cell 120, 261-273.
70. Nagai Y, Yonemitsu S, Erion DM, Iwasaki T, Stark R, Weismann D, Dong J, Zhang D, Jurczak MJ, Loffler MG, et al,. (2009) The role of peroxisome proliferator-activated receptor gamma coactivator-1 beta in the pathogenesis of fructose-induced insulin resistance. Cell Metab 9, 252-264.
71. Chambers KT, Chen Z, Lai L, Leone TC, Towle HC, Kralli A, Crawford PA, &, Finck BN, (2013) PGC-1beta and ChREBP partner to cooperatively regulate hepatic lipogenesis in a glucose concentration-dependent manner. Mol Metab 2, 194-204.
72. Wolfrum C, &, Stoffel M, (2006) Coactivation of Foxa2 through Pgc-1beta promotes liver fatty acid oxidation and triglyceride/VLDL secretion. Cell Metab 3, 99-110.
73. Chambers KT, Chen Z, Crawford PA, Fu X, Burgess SC, Lai L, Leone TC, Kelly DP, &, Finck BN, (2012) Liver-specific PGC-1beta deficiency leads to impaired mitochondrial function and lipogenic response to fasting-refeeding. PLoS One 7, e52645.
74. Watson PA, Reusch JE, McCune SA, Leinwand LA, Luckey SW, Konhilas JP, Brown DA, Chicco AJ, Sparagna GC, Long CS, et al,. (2007) Restoration of CREB function is linked to completion and stabilization of adaptive cardiac hypertrophy in response to exercise. Am J Physiol Heart Circ Physiol 293, H246-259.
75. Lehman JJ, Barger PM, Kovacs A, Saffitz JE, Medeiros DM, &, Kelly DP, (2000) Peroxisome proliferator-activated receptor gamma coactivator-1 promotes cardiac mitochondrial biogenesis. J Clin Invest 106, 847-856.
76. Russell LK, Mansfield CM, Lehman JJ, Kovacs A, Courtois M, Saffitz JE, Medeiros DM, Valencik ML, McDonald JA, &, Kelly DP, (2004) Cardiac-specific induction of the transcriptional coactivator peroxisome proliferator-activated receptor gamma coactivator-1alpha promotes mitochondrial biogenesis and reversible cardiomyopathy in a developmental stage-dependent manner. Circ Res 94, 525-533.
77. Arany Z, He H, Lin J, Hoyer K, Handschin C, Toka O, Ahmad F, Matsui T, Chin S, Wu PH, et al,. (2005) Transcriptional coactivator PGC-1 alpha controls the energy state and contractile function of cardiac muscle. Cell Metab 1, 259-271.
78. Lehman JJ, Boudina S, Banke NH, Sambandam N, Han X, Young DM, Leone TC, Gross RW, Lewandowski ED, Abel ED, et al,. (2008) The transcriptional coactivator PGC-1alpha is essential for maximal and efficient cardiac mitochondrial fatty acid oxidation and lipid homeostasis. Am J Physiol Heart Circ Physiol 295, H185-196.
79. Arany Z, Novikov M, Chin S, Ma Y, Rosenzweig A, &, Spiegelman BM, (2006) Transverse aortic constriction leads to accelerated heart failure in mice lacking PPAR-gamma coactivator 1alpha. Proc Natl Acad Sci USA 103, 10086-10091.
80. Riehle C, Wende AR, Zaha VG, Pires KM, Wayment B, Olsen C, Bugger H, Buchanan J, Wang X, Moreira AB, et al,. (2011) PGC-1beta deficiency accelerates the transition to heart failure in pressure overload hypertrophy. Circ Res 109, 783-793.
81. Lai L, Leone TC, Zechner C, Schaeffer PJ, Kelly SM, Flanagan DP, Medeiros DM, Kovacs A, &, Kelly DP, (2008) Transcriptional coactivators PGC-1alpha and PGC-lbeta control overlapping programs required for perinatal maturation of the heart. Genes Dev 22, 1948-1961.
82. Martin OJ, Lai L, Soundarapandian MM, Leone TC, Zorzano A, Keller MP, Attie AD, Muoio DM, &, Kelly DP, (2014) A Role for Peroxisome Proliferator-Activated Receptor gamma Coactivator-1 in the Control of Mitochondrial Dynamics During Postnatal Cardiac Growth. Circ Res 114, 626-636.
83. Lai L, Wang M, Martin OJ, Leone TC, Vega RB, Han X, &, Kelly DP, (2014) A role for peroxisome proliferator-activated receptor gamma coactivator 1 (PGC-1) in the regulation of cardiac mitochondrial phospholipid biosynthesis. J Biol Chem 289, 2250-2259.
84. Cao W, Daniel KW, Robidoux J, Puigserver P, Medvedev AV, Bai X, Floering LM, Spiegelman BM, &, Collins S, (2004) p38 mitogen-activated protein kinase is the central regulator of cyclic AMP-dependent transcription of the brown fat uncoupling protein 1 gene. Mol Cell Biol 24, 3057-3067.
85. Rim JS, &, Kozak LP, (2002) Regulatory motifs for CREB-binding protein and Nfe2 l2 transcription factors in the upstream enhancer of the mitochondrial uncoupling protein 1 gene. J Biol Chem 277, 34589-34600.
86. Tiraby C, Tavernier G, Lefort C, Larrouy D, Bouillaud F, Ricquier D, &, Langin D, (2003) Acquirement of brown fat cell features by human white adipocytes. J Biol Chem 278, 33370-33376.
87. Kleiner S, Mepani RJ, Laznik D, Ye L, Jurczak MJ, Jornayvaz FR, Estall JL, Chatterjee Bhowmick D, Shulman GI, &, Spiegelman BM, (2012) Development of insulin resistance in mice lacking PGC-1alpha in adipose tissues. Proc Natl Acad Sci USA 109, 9635-9640.
88. Pardo R, Enguix N, Lasheras J, Feliu JE, Kralli A, &, Villena JA, (2011) Rosiglitazone-induced mitochondrial biogenesis in white adipose tissue is independent of peroxisome proliferator-activated receptor gamma coactivator-1alpha. PLoS One 6, e26989.
89. Uldry M, Yang W, St-Pierre J, Lin J, Seale P, &, Spiegelman BM, (2006) Complementary action of the PGC-1 coactivators in mitochondrial biogenesis and brown fat differentiation. Cell Metab 3, 333-341.
90. Enguix N, Pardo R, Gonzalez A, Lopez VM, Simo R, Kralli A, &, Villena JA, (2013) Mice lacking PGC-1beta in adipose tissues reveal a dissociation between mitochondrial dysfunction and insulin resistance. Mol Metab 2, 215-226.
91. Kajimura S, Seale P, &, Spiegelman BM, (2010) Transcriptional control of brown fat development. Cell Metab 11, 257-262.
92. Fisher FM, Kleiner S, Douris N, Fox EC, Mepani RJ, Verdeguer F, Wu J, Kharitonenkov A, Flier JS, Maratos-Flier E, et al,. (2012) FGF21 regulates PGC-1alpha and browning of white adipose tissues in adaptive thermogenesis. Genes Dev 26, 271-281.
93. Wilson-Fritch L, Nicoloro S, Chouinard M, Lazar MA, Chui PC, Leszyk J, Straubhaar J, Czech MP, &, Corvera S, (2004) Mitochondrial remodeling in adipose tissue associated with obesity and treatment with rosiglitazone. J Clin Invest 114, 1281-1289.
94. Bogacka I, Xie H, Bray GA, &, Smith SR, (2005) Pioglitazone induces mitochondrial biogenesis in human subcutaneous adipose tissue in vivo. Diabetes 54, 1392-1399.
95. Rong JX, Qiu Y, Hansen MK, Zhu L, Zhang V, Xie M, Okamoto Y, Mattie MD, Higashiyama H, Asano S, et al,. (2007) Adipose mitochondrial biogenesis is suppressed in db/db and high-fat diet-fed mice and improved by rosiglitazone. Diabetes 56, 1751-1760.
96. St-Pierre J, Drori S, Uldry M, Silvaggi JM, Rhee J, Jager S, Handschin C, Zheng K, Lin J, Yang W, et al,. (2006) Suppression of reactive oxygen species and neurodegeneration by the PGC-1 transcriptional coactivators. Cell 127, 397-408.
97. Egger A, Samardzija M, Sothilingam V, Tanimoto N, Lange C, Salatino S, Fang L, Garcia-Garrido M, Beck S, Okoniewski MJ, et al,. (2012) PGC-1alpha determines light damage susceptibility of the murine retina. PLoS One 7, e31272.
98. Cui S, Tanabe O, Lim KC, Xu HE, Zhou XE, Lin JD, Shi L, Schmidt L, Campbell A, Shimizu R, et al,. (2014) PGC-1 coactivator activity is required for murine erythropoiesis. Mol Cell Biol 34, 1956-1965.
99. Basu S, (2014) A complex interplay between PGC-1 co-activators and mTORC1 regulates hematopoietic recovery following 5-fluorouracil treatment. Stem Cell Res 12, 178-193.
100. Basu S, Broxmeyer HE, &, Hangoc G, (2013) Peroxisome proliferator-activated-gamma coactivator-1alpha-mediated mitochondrial biogenesis is important for hematopoietic recovery in response to stress. Stem Cells Dev 22, 1678-1692.
101. Sonoda J, Laganiere J, Mehl IR, Barish GD, Chong LW, Li X, Scheffler IE, Mock DC, Bataille AR, Robert F, et al,. (2007) Nuclear receptor ERR alpha and coactivator PGC-1 beta are effectors of IFN-gamma-induced host defense. Genes Dev 21, 1909-1920.
102. Vats D, Mukundan L, Odegaard JI, Zhang L, Smith KL, Morel CR, Wagner RA, Greaves DR, Murray PJ, &, Chawla A, (2006) Oxidative metabolism and PGC-1beta attenuate macrophage-mediated inflammation. Cell Metab 4, 13-24.
103. Zamora M, &, Villena JA, (2014) Targeting mitochondrial biogenesis to treat insulin resistance. Curr Pharm Des 20, 5527-5557.
104. Morino K, Petersen KF, Dufour S, Befroy D, Frattini J, Shatzkes N, Neschen S, White MF, Bilz S, Sono S, et al,. (2005) Reduced mitochondrial density and increased IRS-1 serine phosphorylation in muscle of insulin-resistant offspring of type 2 diabetic parents. J Clin Invest 115, 3587-3593.
105. Ritov VB, Menshikova EV, He J, Ferrell RE, Goodpaster BH, &, Kelley DE, (2005) Deficiency of subsarcolemmal mitochondria in obesity and type 2 diabetes. Diabetes 54, 8-14.
106. Dahlman I, Forsgren M, Sjogren A, Nordstrom EA, Kaaman M, Naslund E, Attersand A, &, Arner P, (2006) Downregulation of electron transport chain genes in visceral adipose tissue in type 2 diabetes independent of obesity and possibly involving tumor necrosis factor-alpha. Diabetes 55, 1792-1799.
107. Mootha VK, Lindgren CM, Eriksson KF, Subramanian A, Sihag S, Lehar J, Puigserver P, Carlsson E, Ridderstrale M, Laurila E, et al,. (2003) PGC-1alpha-responsive genes involved in oxidative phosphorylation are coordinately downregulated in human diabetes. Nat Genet 34, 267-273.
108. Patti ME, Butte AJ, Crunkhorn S, Cusi K, Berria R, Kashyap S, Miyazaki Y, Kohane I, Costello M, Saccone R, et al,. (2003) Coordinated reduction of genes of oxidative metabolism in humans with insulin resistance and diabetes: potential role of PGC1 and NRF1. Proc Natl Acad Sci USA 100, 8466-8471.
109. Ek J, Andersen G, Urhammer SA, Gaede PH, Drivsholm T, Borch-Johnsen K, Hansen T, &, Pedersen O, (2001) Mutation analysis of peroxisome proliferator-activated receptor-gamma coactivator-1 (PGC-1) and relationships of identified amino acid polymorphisms to Type II diabetes mellitus. Diabetologia 44, 2220-2226.
110. Hara K, Tobe K, Okada T, Kadowaki H, Akanuma Y, Ito C, Kimura S, &, Kadowaki T, (2002) A genetic variation in the PGC-1 gene could confer insulin resistance and susceptibility to Type II diabetes. Diabetologia 45, 740-743.
111. Vimaleswaran KS, Radha V, Ghosh S, Majumder PP, Deepa R, Babu HN, Rao MR, &, Mohan V, (2005) Peroxisome proliferator-activated receptor-gamma co-activator-1alpha (PGC-1alpha) gene polymorphisms and their relationship to Type 2 diabetes in Asian Indians. Diabet Med 22, 1516-1521.
112. Barres R, Osler ME, Yan J, Rune A, Fritz T, Caidahl K, Krook A, &, Zierath JR, (2009) Non-CpG methylation of the PGC-1alpha promoter through DNMT3B controls mitochondrial density. Cell Metab 10, 189-198.
113. Cohen P, Levy JD, Zhang Y, Frontini A, Kolodin DP, Svensson KJ, Lo JC, Zeng X, Ye L, Khandekar MJ, et al,. (2014) Ablation of PRDM16 and beige adipose causes metabolic dysfunction and a subcutaneous to visceral fat switch. Cell 156, 304-316.
114. Kontani Y, Wang Y, Kimura K, Inokuma KI, Saito M, Suzuki-Miura T, Wang Z, Sato Y, Mori N, &, Yamashita H, (2005) UCP1 deficiency increases susceptibility to diet-induced obesity with age. Aging Cell 4, 147-155.
115. Lowell BB, S-Susulic V, Hamann A, Lawitts JA, Himms-Hagen J, Boyer BB, Kozak LP, &, Flier JS, (1993) Development of obesity in transgenic mice after genetic ablation of brown adipose tissue. Nature 366, 740-742.
116. Choi CS, Befroy DE, Codella R, Kim S, Reznick RM, Hwang YJ, Liu ZX, Lee HY, Distefano A, Samuel VT, et al,. (2008) Paradoxical effects of increased expression of PGC-1alpha on muscle mitochondrial function and insulin-stimulated muscle glucose metabolism. Proc Natl Acad Sci USA 105, 19926-19931.
117. Benton CR, Holloway GP, Han XX, Yoshida Y, Snook LA, Lally J, Glatz JF, Luiken JJ, Chabowski A, &, Bonen A, (2010) Increased levels of peroxisome proliferator-activated receptor gamma, coactivator 1 alpha (PGC-1alpha) improve lipid utilisation, insulin signalling and glucose transport in skeletal muscle of lean and insulin-resistant obese Zucker rats. Diabetologia 53, 2008-2019.
118. Wright LE, Brandon AE, Hoy AJ, Forsberg GB, Lelliott CJ, Reznick J, Lofgren L, Oscarsson J, Stromstedt M, Cooney GJ, et al,. (2011) 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 54, 1417-1426.
119. Chaturvedi RK, &, Flint Beal M, (2013) Mitochondrial diseases of the brain. Free Radic Biol Med 63, 1-29.
120. Katsouri L, Parr C, Bogdanovic N, Willem M, &, Sastre M, (2011) PPARgamma co-activator-1alpha (PGC-1alpha) reduces amyloid-beta generation through a PPARgamma-dependent mechanism. J Alzheimers Dis 25, 151-162.
121. Qin W, Haroutunian V, Katsel P, Cardozo CP, Ho L, Buxbaum JD, &, Pasinetti GM, (2009) PGC-1alpha expression decreases in the Alzheimer disease brain as a function of dementia. Arch Neurol 66, 352-361.
122. Wang R, Li JJ, Diao S, Kwak YD, Liu L, Zhi L, Bueler H, Bhat NR, Williams RW, Park EA, et al,. (2013) Metabolic stress modulates Alzheimer's beta-secretase gene transcription via SIRT1-PPARgamma-PGC-1 in neurons. Cell Metab 17, 685-694.
123. Cui L, Jeong H, Borovecki F, Parkhurst CN, Tanese N, &, Krainc D, (2006) Transcriptional repression of PGC-1alpha by mutant huntingtin leads to mitochondrial dysfunction and neurodegeneration. Cell 127, 59-69.
124. Weydt P, Pineda VV, Torrence AE, Libby RT, Satterfield TF, Lazarowski ER, Gilbert ML, Morton GJ, Bammler TK, Strand AD, et al,. (2006) Thermoregulatory and metabolic defects in Huntington's disease transgenic mice implicate PGC-1alpha in Huntington's disease neurodegeneration. Cell Metab 4, 349-362.
125. Che HV, Metzger S, Portal E, Deyle C, Riess O, &, Nguyen HP, (2011) Localization of sequence variations in PGC-1alpha influence their modifying effect in Huntington disease. Mol Neurodegener 6, 1.
126. Weydt P, Soyal SM, Gellera C, Didonato S, Weidinger C, Oberkofler H, Landwehrmeyer GB, &, Patsch W, (2009) The gene coding for PGC-1alpha modifies age at onset in Huntington's Disease. Mol Neurodegener 4, 3.
127. Dauer W, &, Przedborski S, (2003) Parkinson's disease: mechanisms and models. Neuron 39, 889-909.
128. Zheng B, Liao Z, Locascio JJ, Lesniak KA, Roderick SS, Watt ML, Eklund AC, Zhang-James Y, Kim PD, Hauser MA, et al,. (2010) PGC-1alpha, a potential therapeutic target for early intervention in Parkinson's disease. Sci Transl Med 2, 52ra73.
129. Clark J, Reddy S, Zheng K, Betensky RA, &, Simon DK, (2011) Association of PGC-1alpha polymorphisms with age of onset and risk of Parkinson's disease. BMC Med Genet 12, 69.
130. Mudo G, Makela J, Di Liberto V, Tselykh TV, Olivieri M, Piepponen P, Eriksson O, Malkia A, Bonomo A, Kairisalo M, et al,. (2012) Transgenic expression and activation of PGC-1alpha protect dopaminergic neurons in the MPTP mouse model of Parkinson's disease. Cell Mol Life Sci 69, 1153-1165.
131. Da Cruz S, Parone PA, Lopes VS, Lillo C, McAlonis-Downes M, Lee SK, Vetto AP, Petrosyan S, Marsala M, Murphy AN, et al,. (2012) Elevated PGC-1alpha activity sustains mitochondrial biogenesis and muscle function without extending survival in a mouse model of inherited ALS. Cell Metab 15, 778-786.
132. Zhao W, Varghese M, Yemul S, Pan Y, Cheng A, Marano P, Hassan S, Vempati P, Chen F, Qian X, et al,. (2011) Peroxisome proliferator activator receptor gamma coactivator-1alpha (PGC-1alpha) improves motor performance and survival in a mouse model of amyotrophic lateral sclerosis. Mol Neurodegener 6, 51.
133. Sano M, Wang SC, Shirai M, Scaglia F, Xie M, Sakai S, Tanaka T, Kulkarni PA, Barger PM, Youker KA, et al,. (2004) Activation of cardiac Cdk9 represses PGC-1 and confers a predisposition to heart failure. EMBO J 23, 3559-3569.
134. Bugger H, Chen D, Riehle C, Soto J, Theobald HA, Hu XX, Ganesan B, Weimer BC, &, Abel ED, (2009) Tissue-specific remodeling of the mitochondrial proteome in type 1 diabetic akita mice. Diabetes 58, 1986-1997.
135. Garnier A, Zoll J, Fortin D, N'Guessan B, Lefebvre F, Geny B, Mettauer B, Veksler V, &, Ventura-Clapier R, (2009) Control by circulating factors of mitochondrial function and transcription cascade in heart failure: a role for endothelin-1 and angiotensin II. Circ Heart Fail 2, 342-350.
136. Sebastiani M, Giordano C, Nediani C, Travaglini C, Borchi E, Zani M, Feccia M, Mancini M, Petrozza V, Cossarizza A, et al,. (2007) Induction of mitochondrial biogenesis is a maladaptive mechanism in mitochondrial cardiomyopathies. J Am Coll Cardiol 50, 1362-1369.
137. Sihag S, Cresci S, Li AY, Sucharov CC, &, Lehman JJ, (2009) PGC-1alpha and ERRalpha target gene downregulation is a signature of the failing human heart. J Mol Cell Cardiol 46, 201-212.
138. Karamanlidis G, Nascimben L, Couper GS, Shekar PS, del Monte F, &, Tian R, (2010) Defective DNA replication impairs mitochondrial biogenesis in human failing hearts. Circ Res 106, 1541-1548.
139. Sacheck JM, Hyatt JP, Raffaello A, Jagoe RT, Roy RR, Edgerton VR, Lecker SH, &, Goldberg AL, (2007) Rapid disuse and denervation atrophy involve transcriptional changes similar to those of muscle wasting during systemic diseases. FASEB J 21, 140-155.
140. Sandri M, Lin J, Handschin C, Yang W, Arany ZP, Lecker SH, Goldberg AL, &, Spiegelman BM, (2006) PGC-1alpha protects skeletal muscle from atrophy by suppressing FoxO3 action and atrophy-specific gene transcription. Proc Natl Acad Sci USA 103, 16260-16265.
141. Wenz T, Diaz F, Spiegelman BM, &, Moraes CT, (2008) Activation of the PPAR/PGC-1alpha pathway prevents a bioenergetic deficit and effectively improves a mitochondrial myopathy phenotype. Cell Metab 8, 249-256.
142. Selsby JT, Morine KJ, Pendrak K, Barton ER, &, Sweeney HL, (2012) Rescue of dystrophic skeletal muscle by PGC-1alpha involves a fast to slow fiber type shift in the mdx mouse. PLoS One 7, e30063.
143. Chalkiadaki A, Igarashi M, Nasamu AS, Knezevic J, &, Guarente L, (2014) Muscle-specific SIRT1 gain-of-function increases slow-twitch fibers and ameliorates pathophysiology in a mouse model of duchenne muscular dystrophy. PLoS Genet 10, e1004490.
144. Chan MC, Rowe GC, Raghuram S, Patten IS, Farrell C, &, Arany Z, (2014) Post-natal induction of PGC-1alpha protects against severe muscle dystrophy independently of utrophin. Skelet Muscle 4, 2.
145. Feilchenfeldt J, Brundler MA, Soravia C, Totsch M, &, Meier CA, (2004) Peroxisome proliferator-activated receptors (PPARs) and associated transcription factors in colon cancer: reduced expression of PPARgamma-coactivator 1 (PGC-1). Cancer Lett 203, 25-33.
146. Watkins G, Douglas-Jones A, Mansel RE, &, Jiang WG, (2004) The localisation and reduction of nuclear staining of PPARgamma and PGC-1 in human breast cancer. Oncol Rep 12, 483-488.
147. Zhang Y, Ba Y, Liu C, Sun G, Ding L, Gao S, Hao J, Yu Z, Zhang J, Zen K, et al,. (2007) PGC-1alpha induces apoptosis in human epithelial ovarian cancer cells through a PPARgamma-dependent pathway. Cell Res 17, 363-373.
148. Wirtenberger M, Tchatchou S, Hemminki K, Schmutzhard J, Sutter C, Schmutzler RK, Meindl A, Wappenschmidt B, Kiechle M, Arnold N, et al,. (2006) Associations of genetic variants in the estrogen receptor coactivators PPARGC1A, PPARGC1B and EP300 with familial breast cancer. Carcinogenesis 27, 2201-2208.
149. Jiang WG, Douglas-Jones A, &, Mansel RE, (2003) Expression of peroxisome-proliferator activated receptor-gamma (PPARgamma) and the PPARgamma co-activator, PGC-1, in human breast cancer correlates with clinical outcomes. Int J Cancer 106, 752-757.
150. Burchard J, Zhang C, Liu AM, Poon RT, Lee NP, Wong KF, Sham PC, Lam BY, Ferguson MD, Tokiwa G, et al,. (2010) microRNA-122 as a regulator of mitochondrial metabolic gene network in hepatocellular carcinoma. Mol Syst Biol 6, 402.
151. D'Errico I, Salvatore L, Murzilli S, Lo Sasso G, Latorre D, Martelli N, Egorova AV, Polishuck R, Madeyski-Bengtson K, Lelliott C, et al,. (2011) Peroxisome proliferator-activated receptor-gamma coactivator 1-alpha (PGC1alpha) is a metabolic regulator of intestinal epithelial cell fate. Proc Natl Acad Sci USA 108, 6603-6608.
152. Bhalla K, Hwang BJ, Dewi RE, Ou L, Twaddel W, Fang HB, Vafai SB, Vazquez F, Puigserver P, Boros L, et al,. (2011) PGC1alpha promotes tumor growth by inducing gene expression programs supporting lipogenesis. Cancer Res 71, 6888-6898.
153. LeBleu VS, O'Connell JT, Gonzalez Herrera KN, Wikman H, Pantel K, Haigis MC, de Carvalho FM, Damascena A, Domingos Chinen LT, Rocha RM, et al,. (2014) PGC-1alpha mediates mitochondrial biogenesis and oxidative phosphorylation in cancer cells to promote metastasis. Nat Cell Biol 16, 992-1003, 1001-1015.
154. Deblois G, Chahrour G, Perry MC, Sylvain-Drolet G, Muller WJ, &, Giguere V, (2010) Transcriptional control of the ERBB2 amplicon by ERRalpha and PGC-1beta promotes mammary gland tumorigenesis. Cancer Res 70, 10277-10287.
155. Eichner LJ, Perry MC, Dufour CR, Bertos N, Park M, St-Pierre J, &, Giguere V, (2010) miR-378(∗) mediates metabolic shift in breast cancer cells via the PGC-1beta/ERRgamma transcriptional pathway. Cell Metab 12, 352-361.
156. Mirebeau-Prunier D, Le Pennec S, Jacques C, Gueguen N, Poirier J, Malthiery Y, &, Savagner F, (2010) Estrogen-related receptor alpha and PGC-1-related coactivator constitute a novel complex mediating the biogenesis of functional mitochondria. FEBS J 277, 713-725.
157. Savagner F, Mirebeau D, Jacques C, Guyetant S, Morgan C, Franc B, Reynier P, &, Malthiery Y, (2003) PGC-1-related coactivator and targets are upregulated in thyroid oncocytoma. Biochem Biophys Res Commun 310, 779-784.
158. Miura S, Tomitsuka E, Kamei Y, Yamazaki T, Kai Y, Tamura M, Kita K, Nishino I, &, Ezaki O, (2006) Overexpression of peroxisome proliferator-activated receptor gamma co-activator-1alpha leads to muscle atrophy with depletion of ATP. Am J Pathol 169, 1129-1139.
159. Ciron C, Lengacher S, Dusonchet J, Aebischer P, &, Schneider BL, (2012) Sustained expression of PGC-1alpha in the rat nigrostriatal system selectively impairs dopaminergic function. Hum Mol Genet 21, 1861-1876.
160. Dumont M, Stack C, Elipenahli C, Jainuddin S, Launay N, Gerges M, Starkova N, Starkov AA, Calingasan NY, Tampellini D, et al,. (2014) PGC-1alpha overexpression exacerbates beta-amyloid and tau deposition in a transgenic mouse model of Alzheimer's disease. FASEB J 28, 1745-1755.
161. Vega RB, Huss JM, &, Kelly DP, (2000) 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.
162. Sadana P, Zhang Y, Song S, Cook GA, Elam MB, &, Park EA, (2007) Regulation of carnitine palmitoyltransferase I (CPT-Ialpha) gene expression by the peroxisome proliferator activated receptor gamma coactivator (PGC-1) isoforms. Mol Cell Endocrinol 267, 6-16.
163. Tcherepanova I, Puigserver P, Norris JD, Spiegelman BM, &, McDonnell DP, (2000) Modulation of estrogen receptor-alpha transcriptional activity by the coactivator PGC-1. J Biol Chem 275, 16302-16308.
164. Shao D, Liu Y, Liu X, Zhu L, Cui Y, Cui A, Qiao A, Kong X, Chen Q, Gupta N, et al,. (2010) PGC-1 beta-regulated mitochondrial biogenesis and function in myotubes is mediated by NRF-1 and ERR alpha. Mitochondrion 10, 516-527.
165. Vercauteren K, Gleyzer N, &, Scarpulla RC, (2008) PGC-1-related coactivator complexes with HCF-1 and NRF-2beta in mediating NRF-2(GABP)-dependent respiratory gene expression. J Biol Chem 283, 12102-12111.
166. Vercauteren K, Pasko RA, Gleyzer N, Marino VM, &, Scarpulla RC, (2006) PGC-1-related coactivator: immediate early expression and characterization of a CREB/NRF-1 binding domain associated with cytochrome c promoter occupancy and respiratory growth. Mol Cell Biol 26, 7409-7419.
167. Ichida M, Nemoto S, &, Finkel T, (2002) Identification of a specific molecular repressor of the peroxisome proliferator-activated receptor gamma Coactivator-1 alpha (PGC-1alpha). J Biol Chem 277, 50991-50995.