On the Control of Metabolic Remodeling in Mitochondria of the Failing Heart by Joanne S. Ingwall Circ Heart Fail Volume 2(4):275-277 July 1, 2009 Copyright © American Heart Association, Inc. All rights reserved.

Figure. PGC-1s as master regulators of cardiac metabolism. Figure. PGC-1s as master regulators of cardiac metabolism. Transcriptional activators and coactivators important for long-term molecular remodeling of all aspects of ATP metabolism are shown. MAT1 functions by tethering Cdk7 and cyclin H to PGC-1α, allowing transcription to occur. Each transcriptional family of activators—NRF, ERR, PPAR, RXR, and MEF-2—confer specificity of promoters targeted by PGC-1α, although there is considerable overlap. PGC-1α is activated by p38 MAPK and calcineurin A/CaMKII in response to cold, fasting and growth stimuli. Importantly, PGC-1α is lower in the failing heart. The report by Garnier et al,4 in this issue shows that ET-1 and angiotensin II downregulate whereas aldosterone and isoprenaline upregulate PGC-1α expression in ventricular myocytes. NRF indicates nuclear respiratory factors; ERR, estrogen receptors; PPAR, peroxisome proliferator-activated receptors; RXR, retinoid receptors. Joanne S. Ingwall Circ Heart Fail. 2009;2:275-277 Copyright © American Heart Association, Inc. All rights reserved.