title: Mouse models of mitochondrial dysfunction and heart failure.
abstract: Mitochondria in the adult mammalian heart have a tremendous capacity for oxidative metabolism, and the conversion of energy by these pathways is critical for proper cardiac function. This review describes mouse models relating mitochondrial metabolism to cardiac function through gain- or loss-of-function approaches that manipulate mitochondrial energy transduction or ATP synthetic pathways. Mouse models of mitochondrial defects are relevant to genetic and acquired forms of human cardiomyopathy. Examples include inborn errors in mitochondrial metabolism or end-stage heart failure. Conversely, chronic reliance on energy production via mitochondrial fatty acid oxidation, such as occurs in the diabetic heart, likely leads to maladaptive sequelae including cellular lipotoxicity and mitochondrial dysfunction. Collectively, these model systems have allowed us to begin to dissect the relationship between mitochondrial metabolism and the development of cardiomyopathy and to define the molecular pathways regulating cardiac mitochondrial number and function.
authors.affiliation: Center for Cardiovascular Research, Washington University School of Medicine, 660 South Euclid Avenue, Campus Box 8086, Saint Louis, MO 63110, USA.
authors.forename: Laurie K
authors.initials: LK
authors.lastname: Russell
authors.forename: Brian N
authors.initials: BN
authors.lastname: Finck
authors.forename: Daniel P
authors.initials: DP
authors.lastname: Kelly
mesh_terms: D000818:Animals; D009202:Cardiomyopathies / Q000235:genetics / Q000473:pathology* / Q000503:physiopathology*; D004195:Disease Models, Animal; D005227:Fatty Acids / Q000378:metabolism; D006801:Humans; D051379:Mice; D008929:Mitochondria, Heart / Q000235:genetics / Q000378:metabolism* / Q000473:pathology*; D000071248:Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha; D015534:Trans-Activators / Q000378:metabolism; D014157:Transcription Factors
chemical_list: D005227:Fatty Acids; D000071248:Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha; C485290:Ppargc1a protein, mouse; D015534:Trans-Activators; D014157:Transcription Factors