Regulation of mitochondrial biogenesis and energy metabolism in the heart

ABSTRACT: Mitochondrial homeostasis is regulated by processes such as biogenesis, dynamics, and mitophagy, and is essential for maintaining cardiac function while preserving structural integrity, energy supply, and redox balance. Given their high reliance on mitochondrial adenosine triphosphate generation, cardiomyocytes are particularly vulnerable to mitochondrial dysfunction. In the cardiovascular system, mitochondria respond to various pathophysiological conditions, such as ischemia-reperfusion injury, hypertension, diabetic cardiomyopathy, and heart failure. Mitochondrial impairment drives cardiovascular disease progression through deficient energy production, elevated oxidative stress, activation of inflammatory responses, and programmed cell death. Growing evidence highlights the critical roles of epigenetic and transcriptional networks in the coordinated regulation of mitochondrial biogenesis and metabolism. Targeting these processes is a promising therapeutic strategy to improve mitochondrial health in cardiovascular diseases. This review systematically summarizes recent advances, outlines the key regulatory mechanisms of mitochondrial biogenesis and metabolism, and explores their pathophysiological roles and therapeutic potential.