Role of Mitochondrial Dynamics in Heart Diseases

Abstract

Mitochondrial dynamics, including fission and fusion processes, are essential for heart health. Mitochondria, the powerhouses of cells, maintain their integrity through continuous cycles of biogenesis, fission, fusion, and degradation. Mitochondria are relatively immobile in the adult heart, but their morphological changes due to mitochondrial morphology factors are critical for cellular functions such as energy production, organelle integrity, and stress response. Mitochondrial fusion proteins, particularly Mfn1/2 and Opa1, play multiple roles beyond their pro-fusion effects, such as endoplasmic reticulum tethering, mitophagy, cristae remodeling, and apoptosis regulation. On the other hand, the fission process, regulated by proteins such as Drp1, Fis1, Mff and MiD49/51, is essential to eliminate damaged mitochondria via mitophagy and to ensure proper cell division. In the cardiac system, dysregulation of mitochondrial dynamics has been shown to cause cardiac hypertrophy, heart failure, ischemia/reperfusion injury, and various cardiac diseases, including metabolic and inherited cardiomyopathies. In addition, mitochondrial dysfunction associated with oxidative stress has been implicated in atherosclerosis, hypertension and pulmonary hypertension. Therefore, understanding and regulating mitochondrial dynamics is a promising therapeutic tool in cardiac diseases. This review summarizes the role of mitochondrial morphology in heart diseases for each mitochondrial morphology regulatory gene, and their potential as therapeutic targets to heart diseases.

Keywords: Drp1; Mfn1; Mfn2; Opa1; cardiovascular diseases; fission and fusion; heart failure; mitochondrial dynamics.

Figure 1

Schematic illustration of the mechanism of mitochondrial fission.

Figure 2

Schematic illustration of the mechanism of mitochondrial fusion.

Figure 3

Mitochondrial morphology variation among cells. In cultured cells such as HEK293, neonatal cardiomyocytes and adult cardiomyocytes, mitochondrial morphology is different in the cells. Mitochondrial morphology in neonatal cardiomyocytes is similar to cultured cells. In contrast, adult cardiomyocytes are characterized by smaller, segmented mitochondria.