Mitochondrial Fusion, Fission, and Mitophagy in Cardiac Diseases: Challenges and Therapeutic Opportunities.

Publisher: Mary Ann Liebert, Inc Country of Publication: United States NLM ID: 100888899 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1557-7716 (Electronic) Linking ISSN: 15230864 NLM ISO Abbreviation: Antioxid Redox Signal Subsets: MEDLINE

Original Publication: Larchmont, NY : Mary Ann Liebert, Inc., 1999-

Heart Failure*/metabolism ; Myocardial Infarction*/metabolism; Humans ; Mitochondria/metabolism ; Mitochondrial Dynamics ; Mitophagy

Significance: Mitochondria play a critical role in the physiology of the heart by controlling cardiac metabolism, function, and remodeling. Accumulation of fragmented and damaged mitochondria is a hallmark of cardiac diseases. Recent Advances: Disruption of quality control systems that maintain mitochondrial number, size, and shape through fission/fusion balance and mitophagy results in dysfunctional mitochondria, defective mitochondrial segregation, impaired cardiac bioenergetics, and excessive oxidative stress. Critical Issues: Pharmacological tools that improve the cardiac pool of healthy mitochondria through inhibition of excessive mitochondrial fission, boosting mitochondrial fusion, or increasing the clearance of damaged mitochondria have emerged as promising approaches to improve the prognosis of heart diseases. Future Directions: There is a reasonable amount of preclinical evidence supporting the effectiveness of molecules targeting mitochondrial fission and fusion to treat cardiac diseases. The current and future challenges are turning these lead molecules into treatments. Clinical studies focusing on acute ( i.e ., myocardial infarction) and chronic ( i.e ., heart failure) cardiac diseases are needed to validate the effectiveness of such strategies in improving mitochondrial morphology, metabolism, and cardiac function. Antioxid. Redox Signal. 36, 844-863.

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R01 HL052141 United States HL NHLBI NIH HHS

Keywords: bioenergetic dysfunction; cardiovascular diseases; metabolism; mitochondrial dynamics; oxidative stress; therapy

Date Created: 20220119 Date Completed: 20220511 Latest Revision: 20230502

20240105

PMC9125524

10.1089/ars.2021.0145

35044229