Mitochondrial Ca2+ uptake: tortoise or hare?
Mitochondria are equipped with an efficient machinery for Ca(2+) uptake and extrusion and are capable of storing large amounts of Ca(2+). Furthermore, key steps of mitochondrial metabolism (ATP production) are Ca(2+)-dependent. In the field of cardiac physiology and pathophysiology, two main questions have dominated the thinking about mitochondrial function in the heart: 1) how does mitochondrial Ca(2+) buffering shape cytosolic Ca(2+) levels and affect excitation-contraction coupling, particularly the Ca(2+) transient, on a beat-to-beat basis, and 2) how does mitochondrial Ca(2+) homeostasis influence cardiac energy metabolism. To answer these questions, a thorough understanding of the kinetics of mitochondrial Ca(2+) transport and buffer capacity is required. Here, we summarize the role of mitochondrial Ca(2+) signaling in the heart, discuss the evidence either supporting or arguing against the idea that Ca(2+) can be taken up rapidly by mitochondria during excitation-contraction coupling and highlight some interesting new areas for further investigation.
O'Rourke
Brian
B
Department of Medicine, Division of Cardiology, Johns Hopkins University, Institute of Molecular Cardiobiology, Baltimore, MD 21205-2195, USA. bor@jhmi.edu
Blatter
Lothar A
LA
D000818:Animals; D001692:Biological Transport / Q000502:physiology*; D002118:Calcium / Q000378:metabolism*; D020013:Calcium Signaling / Q000502:physiology; D004734:Energy Metabolism / Q000502:physiology; D006801:Humans; D008928:Mitochondria / Q000378:metabolism* / Q000648:ultrastructure; D051336:Mitochondrial Membranes / Q000378:metabolism; D012964:Sodium / Q000378:metabolism
D012964:Sodium; D002118:Calcium