Peroxisome proliferator-activated receptor gamma coactivator 1-alpha

high-resolution terminology - matching measurements at high-resolution

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

• MitoPedia topic: Genetics - Coactivator

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

Update: 2012-06-06

1. Scarpulla_2011_Biochim Biophys Acta
2. Canto_2009_Nature
3. Casas 2008 PLoS One *
4. Comelli 2011 Mitochondrion *
5. De Cavanagh 2008 Exp Gerontol *
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. Wang 2011 Mol Oncol *

* O2k-Publications