The importance of mitochondrial inner membrane integrity in cardiac homeostasis

Mitochondria are paramount to the metabolism and survival of cardiomyocytes. Mitochondrial Fission Process 1 (MTFP1) is an inner mitochondrial membrane (IMM) protein that is dispensable for mitochondrial division yet essential for the maintenance of mitochondria integrity and cardiac health. Constitutive knockout of MTFP1 in cardiomyocyte of mice results 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 display 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, these data reveal new functions of MTFP1 in the control of bioenergetic efficiency and cell death sensitivity and define its importance in preventing IMM integrity loss and pathogenic cardiac remodeling.