Mitochondrial Ca2+sequestration and precipitation revisited

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.