Resistance of Dynamin-related Protein 1 Oligomers to Disassembly Impairs Mitophagy, Resulting in Myocardial Inflammation and Heart Failure

Abstract

Background: The C452F mutation in the mitochondrial fission protein Drp1 leads to heart failure through an unknown mechanism. Results: C452F impairs Drp1 disassembly, leading to impaired mitophagy, failed bioenergetics, and inflammation. Conclusion: Drp1-mediated mitochondrial fission is essential for normal cardiac function. Significance: Mutations in mitochondrial quality control proteins are a likely cause of human cardiomyopathy.