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

Autor(es)

Scheffer, Debora da Luz ; Garcia, Adriana Ann ; Lee, Lucia ; Mochly-Rosen, Daria ; Ferreira, Julio Cesar Batista

• Tipo de documento: Artigo Científico
• Fonte: Antioxidants & Redox Signaling; v. 36, n. 13, p. 20-pg., 2022-04-18.

Resumo

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. (AU)

• Processo FAPESP: 15/22814-5 - Câncer e coração: novos paradigmas de diagnóstico e tratamento
• Beneficiário: Carlos Eduardo Negrão
• Modalidade de apoio: Auxílio à Pesquisa - Temático
• Processo FAPESP: 19/25049-9 - Peptídeos formilados mitocondriais como moléculas sinalizadoras: nova oportunidade no tratamento da Isquemia/reperfusão cardíaca
• Beneficiário: Julio Cesar Batista Ferreira
• Modalidade de apoio: Auxílio à Pesquisa - Regular
• Processo FAPESP: 18/18627-3 - Mecanismos envolvidos na mitofagia induzida pelo exercício físico: uma nova estratégia no processo de descoberta de fármacos
• Beneficiário: Julio Cesar Batista Ferreira
• Modalidade de apoio: Bolsas no Exterior - Pesquisa
• Processo FAPESP: 13/07937-8 - Redoxoma
• Beneficiário: Ohara Augusto
• Modalidade de apoio: Auxílio à Pesquisa - Centros de Pesquisa, Inovação e Difusão - CEPIDs