The influence of age on the calcium-efflux pathway and matrix calcium buffering power in brain mitochondria.

The variations with age of the ruthenium red-insensitive calcium efflux rate have been studied in rat brain mitochondria. Both H+- and Na+-dependent effluxes are decreased with age when expressed as a function of calcium taken up in mitochondria incubated in the presence of 0.8 mM inorganic phosphate (Pi) and 0.2 mM ADP. However, the age-dependent differences in calcium efflux rates disappear when mitochondria are incubated in the absence of ADP and Pi. It is suggested that the decrease in efflux rate observed with age corresponds to an increased calcium buffering power of the mitochondrial matrix due to an increase in mitochondrial Pi. The causes of the increased Pi accumulation in old-rat-brain mitochondria are yet unknown but possibly not due to differences in the Pi efflux. The results suggest that the age-dependent lowering of the free calcium concentration in the brain mitochondrial matrix together with the reduced activity of the calcium uniporter (Vitórica, J. and Satrústegui, J. (1986) Brain Research 378, 36-48) could lead to an impaired activation of mitochondrial dehydrogenases after a rise in cytosolic calcium.