Mitochondrial Fission Process 1 controls inner membrane integrity and protects against heart failure

Erminia Donnarumma, Michael Kohlhaas, Elodie Vimont, Etienne Kornobis, Thibault Chaze, Quentin Giai Gianetto, Mariette Matondo, Maryse Moya-Nilges, Christoph Maack and Timothy Wai ()
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Erminia Donnarumma: Université Paris Cité
Michael Kohlhaas: University Clinic Würzburg
Elodie Vimont: Université Paris Cité
Etienne Kornobis: Université Paris Cité
Thibault Chaze: Université Paris Cité
Quentin Giai Gianetto: Université Paris Cité
Mariette Matondo: Université Paris Cité
Maryse Moya-Nilges: UTechS, Université Paris Cité
Christoph Maack: University Clinic Würzburg
Timothy Wai: Université Paris Cité

Nature Communications, 2022, vol. 13, issue 1, 1-24

Abstract: 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.

Date: 2022
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DOI: 10.1038/s41467-022-34316-3

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