Calcium and mitochondria

The literature suggests that the physiological functions for which mitochondria sequester Ca2+ are (1) to stimulate and control the rate of oxidative phosphorylation, (2) to induce the mitochondrial permeability transition (MPT) and perhaps apoptotic cell death, and (3) to modify the shape of cytosolic Ca2+ pulses or transients. There is strong evidence that intramitochondrial Ca2+ controls both the rate of ATP production by oxidative phosphorylation and induction of the MPT. Since the results of these processes are so divergent, the signals inducing them must not be ambiguous. Furthermore, as pointed out by Balaban [J. Mol. Cell. Cardiol. 34 (2002 ) 11259–11271], for any repetitive physiological process dependent on intramitochondrial free Ca2+ concentration ([Ca2+]m), a kind of intramitochondrial homeostasis must exist so that Ca2+ influx during the pulse is matched by Ca2+ efflux during the period between pulses to avoid either Ca2+ buildup or depletion. In addition, mitochondrial Ca2+ transport modifies both spatial and temporal aspects of cytosolic Ca2+ signaling. Here, we look at the amounts of Ca2+ necessary to mediate the functions of mitochondrial Ca2+ transport and at the mechanisms of transport themselves in order to set up a hypothesis about how the mechanisms carry out their roles. The emphasis here is on isolated mitochondria and on general mitochondrial properties in order to focus on how mitochondria alone may function to fulfill their physiological roles even though the interactions of mitochondria with other organelles, particularly with endoplasmic and sarcoplasmic reticulum [Sci. STKE re1 (2004) 1–9], may also influence this story.