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- Title
Mitochondrial Fission Process 1 controls inner membrane integrity and protects against heart failure.
- Authors
Donnarumma, Erminia; Kohlhaas, Michael; Vimont, Elodie; Kornobis, Etienne; Chaze, Thibault; Gianetto, Quentin Giai; Matondo, Mariette; Moya-Nilges, Maryse; Maack, Christoph; Wai, Timothy
- Abstract
Mitochondria are paramount to the metabolism and survival of cardiomyocytes. Here we show that Mitochondrial Fission Process 1 (MTFP1) is an inner mitochondrial membrane (IMM) protein that is dispensable for mitochondrial division yet essential for cardiac structure and function. Constitutive knockout of cardiomyocyte MTFP1 in mice resulted in a fatal, adult-onset dilated cardiomyopathy accompanied by extensive mitochondrial and cardiac remodeling during the transition to heart failure. Prior to the onset of disease, knockout cardiac mitochondria displayed specific IMM defects: futile proton leak dependent upon the adenine nucleotide translocase and an increased sensitivity to the opening of the mitochondrial permeability transition pore, with which MTFP1 physically and genetically interacts. Collectively, our data reveal new functions of MTFP1 in the control of bioenergetic efficiency and cell death sensitivity and define its importance in preventing pathogenic cardiac remodeling. Mitochondria power the beating heart. Here, Donnarumma et al. show that loss of the inner mitochondrial membrane protein MTFP1 in cardiomyocytes reduces bioenergetic efficiency and cell death resistance leading to heart failure in mice.
- Subjects
HEART failure; MITOCHONDRIAL membranes; MITOCHONDRIA; MITOCHONDRIAL proteins; MEMBRANE proteins; DILATED cardiomyopathy; PLANT mitochondria
- Publication
Nature Communications, 2022, Vol 13, Issue 1, p1
- ISSN
2041-1723
- Publication type
Article
- DOI
10.1038/s41467-022-34316-3