Transcriptional control of cardiac energy metabolism in health and disease: Lessons from animal models

Biochem Pharmacol. 2024 Mar 30:116185. doi: 10.1016/j.bcp.2024.116185. Online ahead of print.ABSTRACTCardiac ATP production is tightly regulated in order to satisfy the evolving energetic requirements imposed by different cues during health and pathological conditions. In order to sustain high ATP production rates, cardiac cells are endowed with a vast mitochondrial network that is essentially acquired during the perinatal period. Nevertheless, adult cardiac cells also adapt their mitochondrial mass and oxidative function to changes in energy demand and substrate availability by fine-tuning the pathways and mitochondrial machinery involved in energy production. The reliance of cardiac cells on mitochondrial metabolism makes them particularly sensitive to alterations in proper mitochondrial function, so that deficiency in energy production underlies or precipitates the development of heart diseases. Mitochondrial biogenesis is a complex process fundamentally controlled at the transcriptional level by a network of transcription factors and co-regulators, sometimes with partially redundant functions, that ensure adequate energy supply to the working heart. Novel uncovered regulators, such as RIP140, PERM1, MED1 or BRD4 have been recently shown to modulate or facilitate the transcriptional activity of the PGC-1 s/ERRs/PPARs regulatory axis, allowing cardiomyocytes to adapt to a variety of physiological or pathological situations requiring different energy provision. In this revie...
Source: Biochemical Pharmacology - Category: Drugs & Pharmacology Authors: Source Type: research