Peroxisome proliferator-activated receptor gamma coactivator 1-alpha

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Peroxisome proliferator-activated receptor gamma coactivator 1-alpha

Description

Peroxisome proliferator-activated receptor-γ (PPAR-γ) coactivator-1α (PGC-1α) is a protein which functions as an inducible transcriptional coactivator, a coregulator of transcription factors, particularly NRF-1 and TFAM. PGC-1α was first described in 1998 (Puigserver 1998 Cell). PGC-1α drives the formation of slow-twich muscle fibres (Lin 2002 Nature) and is increased upon endurance training (Norrbom 2004 J Appl Physiol). PGC-1α expression is inhibited by the proinflammatory cytokine tumor necrosis factor α (TNF-α) and high levels of leptin. Upregulation of PGC-1α expression is induced by increased eNOS activity -> NO -> guanylate cyclase -> cGMP (Nisoli 2007 Circ Res). AMP-activated protein kinase (AMPK) increases PGC-1α expression through SIRT1 (Canto 2009 Nature).

Abbreviation: PGC-1α

PGC-1α

PGC-1α is a member of the PGC-1 family of coactivators, which includes PGC-1β and PGC-1–related coactivator(PRC). PGC-1α is to be a powerful regulator of energy metabolism under conditions of both health and disease and as such interacts with a broad range of transcription factors that are involved in a wide variety of biological responses including adaptive thermogenesis, mitochondrial biogenesis, glucose and fatty acid metabolism, fiber type switching in skeletal muscle, and heart ontogenesis. In general, PGC-1α is highly expressed in mitochondria-rich tissues with active oxidative metabolism such as brown adipose tissue (BAT), the heart, and skeletal muscle.

Mechanism

By interacting with transcription factors, a transcription coactivator, increases the probability of a gene being transcribed without itself binding to DNA in a sequence-specific manner. Although members of the PGC-1 family lack histone acetyltransferase (HAT) activities, their amino-terminal region interacts with proteins containing HAT activity. The HAT activity of this complex remodels histones within chromatin, leading to enzymatic modification of chromatin, increased access of the RNA polymerase II machinery to RNA, thereby activating target gene transcription.

References including O2k-Publications *

Update: 2012-06-11
  1. Canto 2009 Nature
  2. Casas 2008 PLoS One *
  3. Comelli 2011 Mitochondrion *
  4. De Cavanagh 2008 Exp Gerontol *
  5. Domenis 2012 Int J Mol Sci *
  6. Franko 2012 J Mol Med *
  7. Garcia-Roves 2008 J Biol Chem *
  8. Hempenstall 2012 Mech Ageing Dev *
  9. Hoeks 2012 J Cell Physiol *
  10. Holmstroem 2012 Am J Physiol Endocrinol Metab *
  11. Jorgensen 2009 Am J Physiol Endocrinol Metab *
  12. Jung 2012 J Med Food *
  13. Keeney 2009 Hum Gene Ther *
  14. Lancel 2009 J Pharmacol Exp Ther *
  15. Lin 2002 Nature
  16. Mirebeau-Prunier 2010 FEBS J *
  17. Nisoli 2007 Circ Res
  18. Lin 2005 Cell Metab
  19. Norrbom 2004 J Appl Physiol
  20. Puigserver 1998 Cell
  21. Remels 2010 FASEB J *
  22. Scarpulla 2011 Biochim Biophys Acta
  23. Wang 2011 Mol Oncol *