Regulation of mitochondrial fission by Drp1 in cardiomyopathy: possible mechanisms linking cellular processes to cell death.

Cardiomyopathy is a common cause of morbidity and mortality worldwide. Its incidence is increasing and is exacerbated by medical conditions, including myocardial ischemia, insulin resistance, obesity, aging, and hypertension. Consequently, improving patient outcomes requires the identification of new therapeutic goals that can stop the emergence and worsening of cardiomyopathy. Additionally, normal heart contractile activity depends on the synthesis of adenosine triphosphate (ATP), which is mostly dependent on cardiac mitochondria. The term “mitochondrial dynamics” describes the highly dynamic nature of mitochondria, which undergo fission and fusion to alter their morphology, distribution and function. Drp1, or dynamin-related protein 1, is necessary for mitochondrial fission, and its function is meticulously controlled to eliminate damaged mitochondria via mitophagy. This process is essential for maintaining the precise regulation of organ and cellular activities in the heart. Many changes occur after posttranslational modifications (PTMs) of Drp1 have been found. These include palmitoylation, phosphorylation, SUMOylation, ubiquitination, S-nitrosylation, O-GlcNAcylation, and acetylation. All these changes help control mitochondrial function. Furthermore, the heart’s ability to contract and the metabolism of cardiomyocytes depend on the dynamic regulation of mitochondrial homeostasis, whereas the pathophysiology of various cardiomyopathies is largely attributed to deficiencies in mitochondrial dynamics. This study explored the role of Drp1 in autophagy, mitophagy, apoptosis, and calcium overload in cardiomyopathies. It also provides an overview of what is currently known about the critical function that Drp1 plays in the development of cardiomyopathies. We further emphasized the possible therapeutic advantages of focusing on Drp1 in the treatment of cardiomyopathy.