title: Mitochondrial dynamism and cardiac fate--a personal perspective.
abstract: Defects in mitochondrial biogenesis are well known to contribute to cardiac dysfunction. By contrast, mechanistic details of essential homeostatic mechanisms that maintain mitochondrial health in the heart are only recently being uncovered, and the pathological potential of these processes is largely hypothetical. I will review the role of mitochondrial dynamics, focusing on cyclic organelle fission and fusion, in normal and diseased hearts. Special attention is given to recent insights into the non-canonical functioning of the mitofusin 2 (Mfn2) outer mitochondrial membrane fusion protein as a regulator of sarcoplasmic-reticular calcium crosstalk and a critical determinant of mitophagic culling of damaged mitochondria. Because mitochondrial fusion in normal adult cardiomyocytes occurs so slowly and infrequently, I postulate that the major function of Mfn2 in the heart may not be to redundantly promote mitochondrial fusion with Mfn1, but to centrally orchestrate mitochondrial quality control.
authors.affiliation: Center for Pharmacogenomics, Department of Internal Medicine, Washington University School of Medicine, St. Louis, MO 63110, USA. gdorn@dom.wustl.edu
authors.forename: Gerald W
authors.initials: GW
authors.lastname: Dorn
mesh_terms: D000818:Animals; D002118:Calcium / Q000378:metabolism; D020558:GTP Phosphohydrolases / Q000378:metabolism*; D006331:Heart Diseases / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D006801:Humans; D008929:Mitochondria, Heart / Q000378:metabolism* / Q000473:pathology; D063154:Mitochondrial Dynamics; D033681:Mitochondrial Membrane Transport Proteins / Q000378:metabolism; D024101:Mitochondrial Proteins / Q000378:metabolism*; D032383:Myocytes, Cardiac / Q000378:metabolism* / Q000473:pathology; D012519:Sarcoplasmic Reticulum / Q000378:metabolism
chemical_list: D033681:Mitochondrial Membrane Transport Proteins; D024101:Mitochondrial Proteins; D020558:GTP Phosphohydrolases; C470018:MFN2 protein, human; C470017:Mfn1 protein, human; D002118:Calcium