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

Thomas J. Cahill, Vincenzo Leo, Matthew Kelly, Alexander Stockenhuber, Nolan W. Kennedy, Leyuan Bao, Grazia Cereghetti, Andrew R. Harper, Gabor Czibik, Chunyan Lao, Mohamed Bellahcene, Violetta Steeples, Safar Ghaffari, Arash Yavari, Alice Mayer, Joanna Poulton, David J.P. Ferguson, Luca Scorrano, Nishani T. Hettiarachchi, Chris Peers & 6 others John Boyle, R. Blake Hill, Alison Simmons, Hugh Watkins, Terence Neil Dear, Houman Ashrafian

Research output: Contribution to journalArticle

25 Citations (Scopus)

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.

LanguageEnglish
Pages25907-25919
Number of pages13
JournalJournal of Biological Chemistry
Volume290
Issue number43
DOIs
Publication statusPublished - 23 Oct 2015

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

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