Mitochondrial Ca2+ sequestration and precipitation revisited

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The ability of mitochondria to sequester and retain divalent cations in the form of precipitates consisting of organic and inorganic moieties has been known for decades. Of these cations, Ca2+ has emerged as a major player in both signal transduction and cell death mechanisms, and, as a consequence, the importance of mitochondria in these processes was soon recognized. Early studies showed considerable effort in identifying the mechanisms of Ca2+ sequestration, precipitation and release by uncouplers of oxidative phosphorylation; however, relatively little information was obtained, and these processes were eventually taken for granted. Here, we re-examine: (a) the thermodynamic aspects of mitochondrial Ca2+ uptake and release, (b) the insufficiently explained effect of uncouplers in inducing mitochondrial Ca2+ release, (c) the thermodynamic effects of exogenously added adenine nucleotides on mitochondrial Ca2+ uptake capacity and precipitate formation, and (d) the elusive nature of the Ca2+-phosphate precipitates formed in the mitochondrial matrix.

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