Regulation of mitochondrial Ca2+ and its effects on energetics and redox balance in normal and failing heart.
Ca(2+) has been well accepted as a signal that coordinates changes in cytosolic workload with mitochondrial energy metabolism in cardiomyocytes. During increased work, Ca(2+) is accumulated in mitochondria and stimulates ATP production to match energy supply and demand. The kinetics of mitochondrial Ca(2+) ([Ca(2+)](m)) uptake remains unclear, and we review the debate on this subject in this article. [Ca(2+)](m) has multiple targets in oxidative phosphorylation including the F1/FO ATPase, the adenine nucleotide translocase, and Ca(2+)-sensitive dehydrogenases (CaDH) of the tricarboxylic acid (TCA) cycle. The well established effect of [Ca(2+)](m) is to activate CaDHs of the TCA cycle to increase NADH production. Maintaining NADH level is not only critical to keep a high oxidative phosphorylation rate during increased cardiac work, but is also necessary for the reducing system of the cell to maintain its reactive oxygen species (ROS) -scavenging capacity. Further, we review recent data demonstrating the deleterious effects of elevated Na(+) in cardiac pathology by blunting [Ca(2+)](m) accumulation.
Liu
Ting
T
Institute of Molecular Cardiobiology, Division of Cardiology, The Johns Hopkins University, Baltimore, MD, USA.
O'Rourke
Brian
B
D000255:Adenosine Triphosphate / Q000096:biosynthesis*; D000818:Animals; D002118:Calcium; D002952:Citric Acid Cycle; D006333:Heart Failure / Q000378:metabolism*; D006801:Humans; D008929:Mitochondria, Heart / Q000378:metabolism* / Q000473:pathology; D000226:Mitochondrial ADP, ATP Translocases / Q000378:metabolism; D009206:Myocardium / Q000378:metabolism* / Q000473:pathology; D009243:NAD / Q000096:biosynthesis; D010084:Oxidation-Reduction; D010085:Oxidative Phosphorylation; D006180:Proton-Translocating ATPases / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000378:metabolism; D012964:Sodium / Q000378:metabolism
D017382:Reactive Oxygen Species; D009243:NAD; D000255:Adenosine Triphosphate; D000226:Mitochondrial ADP, ATP Translocases; D012964:Sodium; D006180:Proton-Translocating ATPases; D002118:Calcium