Abstract

Healthy mitochondrial function is imperative for most tissues, but especially those with a high energy demand. Robust evidence linking mitochondrial dysfunction with cardiovascular disease has demonstrated that mitochondrial activity is highly relevant to cardiac muscle performance. Mitochondrial homeostasis is maintained through coordination among the processes that comprise the so-called mitochondrial dynamics machinery. The most-studied elements of cardiac mitochondrial dynamics are mitochondrial fission and fusion, biogenesis and degradation. Selective autophagic removal of mitochondria (mitophagy) is essential for clearing away defective mitochondria but can lead to cell damage and death if not tightly controlled. In cardiovascular cells such as cardiomyocytes and cardiac fibroblasts, mitophagy is involved in metabolic activity, cell differentiation, apoptosis and other physiological processes related to major phenotypic changes. Modulation of mitophagy has detrimental and/or beneficial outcomes in various cardiovascular diseases, suggesting that a deeper understanding of the mechanisms underlying mitochondrial degradation in the heart could provide valuable clinical insights. Here, we discuss current evidence supporting the role of mitophagy in cardiac pathophysiology, with an emphasis on different research models and their interpretations; basic concepts related to this selective autophagy; and the most commonly used experimental approaches for studying this mechanism. Finally, we provide a comprehensive literature analysis on the role of mitophagy in heart failure, ischemia/reperfusion, diabetic cardiomyopathy and other cardiovascular diseases, as well as its potential biomedical applications.