Mouse models of mitochondrial dysfunction and heart failure

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 Examples include inborn errors in mitochondrial mitochondrial defects are relevant to genetic and acquired forms of human cardiomyopathy 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. (C) 2004 Elsevier Ltd. All rights reserved.