Post-Translational Modifications of Mitochondrial Fission and Fusion Proteins in Cardiac Physiology and Pathophysiology.

Mitochondrial fragmentation frequently occurs in chronic pathological conditions as seen in various human diseases. In fact, abnormal mitochondrial morphology and mitochondrial dysfunction are hallmarks of heart failure (HF) in both human patients and HF animal models. A link between mitochondrial fragmentation and cardiac pathologies has widely been proposed, but the physiological relevance of mitochondrial fission/fusion in the heart is still unclear. Recent studies have increasingly shown that post-translational modifications (PTMs) of fission/fusion proteins are capable of directly modulating the stability, localization, and/or activity of these proteins. These PTMs include phosphorylation, acetylation, ubiquitination, SUMOylation, and O-linked-N-acetyl-glucosamine glycosylation, and proteolysis. Thus, understanding the PTMs of fission/fusion proteins may allow us to understand the complexities that determine the balance of mitochondrial fission and fusion as well as mitochondrial function in various cell-types/organs including cardiomyocytes/heart. In this review, we summarize the current knowledge regarding the function and regulation of mitochondrial fission and fusion in cardiomyocytes, specifically focusing on the PTMs of each mitochondrial fission/fusion protein. We also discuss the molecular mechanisms underlying abnormal mitochondrial morphology in HF and their contributions to the development of cardiac diseases, highlighting the crucial roles of PTMs of mitochondrial fission/fusion proteins. Lastly, we discuss the future potential of manipulating PTMs of fission/fusion proteins as a therapeutic strategy for preventing and/or treating HF.