Activation of PPARGC1A (PGC-1alpha) by phosphorylation

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R-HSA-2151209
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Homo sapiens
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The transcriptional coactivator PPARGC1A (PGC-1alpha), one of the master regulators of mitochondrial biogenesis, is activated by phosphorylation. Energy depletion causes a reduction in ATP and an increase in AMP which activates AMPK. AMPK in turn phosphorylates PPARGC1A. Likewise, p38 MAPK is activated by muscle contraction (possibly via calcium and CaMKII) and phosphorylates PPARGC1A. PPARGC1A does not bind DNA directly, but rather interacts with other transcription factors. Deacetylation of PPARGC1A by SIRT1 appears to follow phosphorylation however the role of deacetylation is unresolved (Canto et al. 2009, Gurd et al. 2011, Philp et al. 2011)

Literature References
PubMed ID Title Journal Year
20933024 Metabolic control of mitochondrial biogenesis through the PGC-1 family regulatory network

Scarpulla, RC

Biochim Biophys Acta 2011
19276888 PGC-1alpha, SIRT1 and AMPK, an energy sensing network that controls energy expenditure

Cantó, C, Auwerx, J

Curr Opin Lipidol 2009
21543634 Nuclear SIRT1 activity, but not protein content, regulates mitochondrial biogenesis in rat and human skeletal muscle

Gurd, BJ, Yoshida, Y, McFarlan, JT, Holloway, GP, Moyes, CD, Heigenhauser, GJ, Spriet, L, Bonen, A

Am J Physiol Regul Integr Comp Physiol 2011
21757760 Sirtuin 1 (SIRT1) Deacetylase Activity Is Not Required for Mitochondrial Biogenesis or Peroxisome Proliferator-activated Receptor-{gamma} Coactivator-1{alpha} (PGC-1{alpha}) Deacetylation following Endurance Exercise

Philp, A, Chen, A, Lan, D, Meyer, GA, Murphy, AN, Knapp, AE, Olfert, IM, McCurdy, CE, Marcotte, GR, Hogan, MC, Baar, K, Schenk, S

J Biol Chem 2011
19262508 AMPK regulates energy expenditure by modulating NAD+ metabolism and SIRT1 activity

Cantó, C, Gerhart-Hines, Z, Feige, JN, Lagouge, M, Noriega, L, Milne, JC, Elliott, PJ, Puigserver, P, Auwerx, J

Nature 2009
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