Regulation of Hypoxia-Inducible Genes by PGC-1α by Jonathan Shoag, and Zolt Arany Arterioscler Thromb Vasc Biol Volume 30(4):662-666 April 1, 2010 Copyright © American Heart Association, Inc. All rights reserved.

Figure. Tissue hypoxia and nutrient deprivation, stemming from vascular disease and other insults, blocks the degradation of HIF-1 (1), leading to activation of the HRE and induction of VEGF. Independently of HIF, PGC-1 is also induced (2), by mechanisms still unclear. Figure. Tissue hypoxia and nutrient deprivation, stemming from vascular disease and other insults, blocks the degradation of HIF-1 (1), leading to activation of the HRE and induction of VEGF. Independently of HIF, PGC-1 is also induced (2), by mechanisms still unclear. PGC-1 then binds to ERR on the promoter and a novel enhancer in the first intron of the VEGF gene, leading to robust gene activation (3). The relationship between HIF-1 and PGC-1/ERR, if any, remains incompletely defined (4). Other genes are also activated by PGC-1 (5), contributing to the response to ischemia. The normal ability of PGC-1 to induce mitochondrial proliferation is blocked in ischemia, by unclear means (6). It is also possible that in some contexts, mitochondrial biogenesis does occur, and that excess mitochondrial activity leads to local hypoxia (7), in turn indirectly leading to HIF activation. Jonathan Shoag, and Zolt Arany Arterioscler Thromb Vasc Biol. 2010;30:662-666 Copyright © American Heart Association, Inc. All rights reserved.