description
Mitochondrial biogenesis and remodeling occur in response to exercise and redox state (reviewed in Scarpulla et al. 2012, Handy and Loscalzo 2012, Piantadosi and Suliman 2012, Scarpulla 2011, Wenz et al. 2011, Bo et al. 2010, Jornayvaz and Shulman 2010, Ljubicic et al. 2010, Hock and Kralli 2009, Canto and Auwerx 2009, Lin 2009, Scarpulla 2008, Ventura-Clapier et al. 2008). It is hypothesized that calcium influx and energy depletion are the signals that initiate changes in gene expression leading to new mitochondrial proteins. Energy depletion causes a reduction in ATP and an increase in AMP which activates AMPK. AMPK in turn phosphorylates the coactivator PGC-1alpha (PPARGC1A), one of the master regulators of mitochondrial biosynthesis. Likewise, p38 MAPK is activated by muscle contraction (possibly via calcium and CaMKII) and phosphorylates PGC-1alpha. CaMKIV responds to intracellular calcium by phosphorylating CREB, which activates expression of PGC-1alpha.Deacetylation of PGC-1alpha by SIRT1 may also play a role in activation (Canto et al. 2009, Gurd et al. 2011), however Sirt11 deacetylation of Ppargc1a in mouse impacted genes related to glucose metabolism rather than mitochondrial biogenesis (Rodgers et al. 2005) and mice lacking SIRT1 in muscle had normal levels of mitochondrial biogenesis in response to exercise (Philp et al. 2011) so the role of deacetylation is not fully defined. PGC-1beta and PPRC appear to act similarly to PGC-1alpha but they have not been as well studied.Phosphorylated PGC-1alpha does not bind DNA directly but instead interacts with other transcription factors, notably NRF1 and NRF2 (via HCF1). NRF1 and NRF2 together with PGC-1alpha activate the transcription of nuclear-encoded, mitochondrially targeted proteins such as TFB2M, TFB1M, and TFAM

external resources
NCBI:1268839
REACTOME:R-HSA-1592230
PUBMED:18430751
PUBMED:19262508
PUBMED:22265687
PUBMED:20533901
PUBMED:20933024
PUBMED:21757760
PUBMED:19575678
PUBMED:19008463
PUBMED:21629705
PUBMED:21543634
PUBMED:22817841
PUBMED:20649548
PUBMED:22146081
PUBMED:19276888
PUBMED:19682549
PUBMED:15744310
PUBMED:19076454

genes
ALAS1 , ATP5F1B , CREB1 , ATF2 , CREBBP , MAPK14 , ESRRA , GABPA , GABPB1 , HCFC1 , MEF2C , MEF2D , NRF1 , POLRMT , PPARA , MED1 , PRKAA2 , PRKAB1 , PRKAB2 , PRKAG1 , MAPK11 , RXRA , MAPK12 , SMARCD3 , SSBP1 , TBL1X , TFAM , MTERF1 , NCOA1 , HDAC3 , NR1D1 , NCOR1 , CARM1 , NCOA2 , PPARGC1A , POLG2 , NCOA6 , PPRC1 , CRTC1 , SIRT3 , TFB1M , PRKAG2 , PRKAG3 , CYCS , GABPB1-IT1 , TWNK , TFB2M , CRTC3 , TBL1XR1 , CHD9 , HELZ2 , TGS1 , PPARGC1B , CRTC2 ,