The role of mitochondrial fission in cardiovascular health and disease

• Published in: Nature reviews cardiology Vol. 19; no. 11; pp. 723 - 736
• Main Authors: Quiles, Justin M., Gustafsson, Åsa B.
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 01-11-2022; Nature Publishing Group
• Subjects: 631/80/642/333; 692/4019/592/75; Actins; Adenosine Triphosphate; Autophagy; Cardiac Imaging; Cardiac Surgery; Cardiology; Cardiomyopathy; Cardiovascular disease; Cell cycle; Dynamins - metabolism; Fibroblasts; Genotype & phenotype; GTP Phosphohydrolases - metabolism; Heart failure; Homeostasis; Humans; Medicine; Medicine & Public Health; Mitochondria; Mitochondrial DNA; Mitochondrial Dynamics - physiology; Morphology; Proteins; Recruitment; Review Article; Transgenic animals
• ISSN: 1759-5002; 1759-5010
• DOI: 10.1038/s41569-022-00703-y

Mitochondria are organelles involved in the regulation of various important cellular processes, ranging from ATP generation to immune activation. A healthy mitochondrial network is essential for cardiovascular function and adaptation to pathological stressors. Mitochondria undergo fission or fusion in response to various environmental cues, and these dynamic changes are vital for mitochondrial function and health. In particular, mitochondrial fission is closely coordinated with the cell cycle and is linked to changes in mitochondrial respiration and membrane permeability. Another key function of fission is the segregation of damaged mitochondrial components for degradation by mitochondrial autophagy (mitophagy). Mitochondrial fission is induced by the large GTPase dynamin-related protein 1 (DRP1) and is subject to sophisticated regulation. Activation requires various post-translational modifications of DRP1, actin polymerization and the involvement of other organelles such as the endoplasmic reticulum, Golgi apparatus and lysosomes. A decrease in mitochondrial fusion can also shift the balance towards mitochondrial fission. Although mitochondrial fission is necessary for cellular homeostasis, this process is often aberrantly activated in cardiovascular disease. Indeed, strong evidence exists that abnormal mitochondrial fission directly contributes to disease development. In this Review, we compare the physiological and pathophysiological roles of mitochondrial fission and discuss the therapeutic potential of preventing excessive mitochondrial fission in the heart and vasculature.
In this Review, Quiles and Gustafsson compare the physiological and pathophysiological roles of mitochondrial fission and discuss the therapeutic potential of preventing excessive mitochondrial fission in the heart and vasculature.
Key points
Mitochondria are involved in regulating many important cellular processes, including metabolism, ATP generation, immune response and activation of cell death pathways.
Mitochondria are dynamic and undergo changes in morphology in response to various environmental cues, which affects organelle function.
Mitochondrial fission is subject to sophisticated regulation, and activation involves various post-translational modifications of dynamin-related protein 1 (DRP1), actin polymerization, and the involvement of other organelles.
Although mitochondrial fission is crucial for cardiac homeostasis, strong evidence indicates that dysregulation of DRP1-mediated fission contributes to the development of several cardiovascular pathologies.
Targeting proteins that regulate mitochondrial dynamics has strong therapeutic potential for cardiovascular disease.