The mitochondrial translocator protein and arrhythmogenesis in ischemic heart disease.
Mitochondrial dysfunction is a hallmark of multiple cardiovascular disorders, including ischemic heart disease. Although mitochondria are well recognized for their role in energy production and cell death, mechanisms by which they control excitation-contraction coupling, excitability, and arrhythmias are less clear. The translocator protein (TSPO) is an outer mitochondrial membrane protein that is expressed in multiple organ systems. The abundant expression of TSPO in macrophages has been leveraged to image the immune response of the heart to inflammatory processes. More recently, the recognition of TSPO as a regulator of energy-dissipating mitochondrial pathways has extended its utility from a diagnostic marker of inflammation to a therapeutic target influencing diverse pathophysiological processes. Here, we provide an overview of the emerging role of TSPO in ischemic heart disease. We highlight the importance of TSPO in the regenerative process of reactive oxygen species (ROS) induced ROS release through its effects on the inner membrane anion channel (IMAC) and the permeability transition pore (PTP). We discuss evidence implicating TSPO in arrhythmogenesis in the settings of acute ischemia-reperfusion injury and myocardial infarction.
Cardiovascular Institute, Icahn School of Medicine at Mount Sinai, Hess Center for Science & Medicine, One Gustave L. Levy Place, P.O. Box 1030, New York, NY 1002, USA.
Lukas J
0000-0003-2832-6582
LJ
Motloch
Cardiovascular Institute, Icahn School of Medicine at Mount Sinai, Hess Center for Science & Medicine, One Gustave L. Levy Place, P.O. Box 1030, New York, NY 1002, USA.
Jun
0000-0002-7013-0703
J
Hu
Cardiovascular Institute, Icahn School of Medicine at Mount Sinai, Hess Center for Science & Medicine, One Gustave L. Levy Place, P.O. Box 1030, New York, NY 1002, USA.
Fadi G
FG
Akar
D006801:Humans; D007473:Ion Channels / Q000378:metabolism; D008928:Mitochondria / Q000378:metabolism*; D033681:Mitochondrial Membrane Transport Proteins / Q000378:metabolism*; D000083162:Mitochondrial Permeability Transition Pore; D017202:Myocardial Ischemia / Q000378:metabolism / Q000473:pathology*; D018384:Oxidative Stress; D017382:Reactive Oxygen Species / Q000378:metabolism
D007473:Ion Channels; D033681:Mitochondrial Membrane Transport Proteins; D000083162:Mitochondrial Permeability Transition Pore; D017382:Reactive Oxygen Species