It has been firmly established that the rapid uptake of Ca2+ by mitochondria from a wide range of sources is mediated by a uniporter which permits transport of the ion down its electrochemical gradient. Several mechanisms of Ca2+ efflux from mitochondria have also been extensively discussed in the literature. Energized mitochondria must expend a significant amount of energy to transport Ca2+ against its electrochemical gradient from the matrix space to the external space. Two separate mechanisms have been found to mediate this outward transport: a Ca2+/nNa+ exchanger and a Na(+)-independent efflux mechanism. These efflux mechanisms are considered from the perspective of available energy. In addition, a reversible Ca2(+)-induced increase in inner membrane permeability can also occur. The induction of this permeability transition is characterized by swelling of the mitochondria, leakiness to small ions such as K+, Mg2+, and Ca2+, and loss of the mitochondrial membrane potential. It has been suggested that the permeability transition and its reversal may also function as a mitochondrial Ca2+ efflux mechanism under some conditions. The characteristics of each of these mechanisms are discussed, as well as their possible physiological functions.

Mechanisms by which mitochondria transport calcium.

This review provides a selective history of how studies of mitochondrial cation transport (K+, Na+, Ca2+) developed in relation to the major themes of research in bioenergetics. It then covers in some detail specific transport pathways for these cations, and it introduces and discusses open problems about their nature and physiological function, particularly in relation to volume regulation and Ca2+homeostasis. The review should provide the basic elements needed to understand both earlier mitochondrial literature and current problems associated with mitochondrial transport of cations and hopefully will foster new interest in the molecular definition of mitochondrial cation channels and exchangers as well as their roles in cell physiology.

http://agrino.org/skalifourta/Mitochondrial%20Transport%20of%20Cations-%20Channels,%20Exchangers,%20and%20Permeability%20Transition.pdf

Mitochondrial Transport of Cations: Channels, Exchangers, and Permeability Transition

Decoding of cytosolic calcium oscillations in the mitochondria

Although it has been known for over three decades that mitochondria are endowed with a complex array of Ca2+ transporters and that key enzymes of mitochondrial metabolism are regulated by Ca2+, the possibility that physiological stimuli that raise the [Ca2+] of the cytoplasm could trigger major mitochondrial Ca2+ uptake has long been considered unlikely, based on the low affinity of the mitochondrial transporters and the limited amplitude of the cytoplasmic [Ca2+] rises The direct measurement of mitochondrial [Ca2+] with highly selective probes has led to a complete reversion of this view, by demonstrating that, after cell stimulation, the cytoplasmic Ca2+ signal is always paralleled by a much larger rise in [Ca2+] in the mitochondrial matrix This observation has rejuvenated the study of mitochondrial Ca2+ transport and novel, unexpected results have altered long-standing dogmas in the field of calcium signalling Here we focus on four main topics: (i) the current knowledge of the functional properties of the Ca2+ transporters and of the thermodynamic constraints under which they operate; (ii) the occurrence of mitochondrial Ca2+ uptake in living cells and the key role of local signalling routes between the mitochondria and the Ca2+ sources; (iii) the physiological consequences of Ca2+ transport for both mitochondrial function and the modulation of the cytoplasmic Ca2+ signal; and (iv) evidence that alterations of mitochondrial Ca2+ signalling may occur in pathophysiological conditions

Mitochondria as all-round players of the calcium game.

Mitochondrial calcium transport: mechanisms and functions.

Ca2+ ions, an allosteric activator of calcium uptake in rat liver mitochondria

Spermine, another specific allosteric activator of calcium uptake in rat liver mitochondria

Rat liver mitochondria are able to temporarily lower the steady-state concentration of external Ca2+ after having accumulated a pulse of added Ca2+. This has been attributed to inhibition of a putative delta psi-modulated efflux pathway [Bernardi, P. (1984) Biochim. Biophys. Acta 766, 277-282]. On the other hand, the rebounding could be due to stimulation of the uniporter by Ca2+ [Kroner, H. (1987) Biol. Chem. Hoppe-Seyler 369, 149-155]. By measuring unidirectional Ca2+ fluxes, it was found that the uniporter was stimulated during the rebounding peak both under Bernardi's and Kroner's conditions, while no effects on the efflux could be demonstrated. The rate of unidirectional efflux of Ca2+ was not affected by inhibition of the uniporter. It appears likely that the rebounding is due to stimulation of the uniporter rather than inhibition of efflux.

Hans Kröner

Papers

Ca2+ ions, an allosteric activator of calcium uptake in rat liver mitochondria

Spermine, another specific allosteric activator of calcium uptake in rat liver mitochondria

Regulation of Ca2+ fluxes in rat liver mitochondria by Ca2+. Effects on Ca2+ distribution.