title: Mitochondrial involvement in myocyte death and heart failure.
abstract: As the heart is an energy-demanding organ, impaired cardiac energy metabolism and mitochondrial function have been inexorably linked to cardiac dysfunction. There is a growing recognition that mitochondrial dysfunction contributes to impaired myocardial energetics and increased oxidative stress in cardiomyopathies, cardiac ischemic damage and heart failure (HF), and mitochondrial permeability transition pore opening has been reported a critical trigger of myocyte death and myocardial remodeling. It is well established that mitochondria play pivotal roles in intracellular signaling in both cell death as well as in cardioprotective pathways. Moreover, recent studies have shown that defects in mitochondrial dynamics affecting biogenesis and turnover are linked to cardiac senescence and HF. Accordingly, there has been an increasing interest in targeting mitochondria for HF therapy. This article reviews the background and recent evidence of mitochondrial involvement in several types of cell death (apoptosis, necrosis and autophagy) occurring in HF. In addition, potential strategies for targeting mitochondria are examined, and their utility in HF therapy considered.
authors.affiliation: St. Christopher's Hospital for Children, Drexel University College of Medicine, Philadelphia, PA, 19134, USA. migojo2@yahoo.com.
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Goldenthal
mesh_terms: D016923:Cell Death; D004734:Energy Metabolism; D006333:Heart Failure / Q000503:physiopathology* / Q000628:therapy; D006801:Humans; D008929:Mitochondria, Heart / Q000378:metabolism*; D033681:Mitochondrial Membrane Transport Proteins; D000083162:Mitochondrial Permeability Transition Pore; D032383:Myocytes, Cardiac / Q000378:metabolism*; D018384:Oxidative Stress; D016032:Randomized Controlled Trials as Topic; D017382:Reactive Oxygen Species / Q000378:metabolism
chemical_list: D033681:Mitochondrial Membrane Transport Proteins; D000083162:Mitochondrial Permeability Transition Pore; D017382:Reactive Oxygen Species
keywords: Apoptosis; Autophagy; Mitochondria; Necrosis; Permeability; Pore