The pyruvate, NAD +-isocitrate and 2-oxoglutarate dehydrogenases are key regulatory enzymes in intramitochondrial oxidative metabolism in mammalian tissues, and can all be activated by increases in Ca 2+ in the micromolar range. There is now mounting evidence that hormones and other stimuli which act by increasing cytosolic Ca 2+ also, as a result, cause increases in mitochondrial matrix Ca 2+ and hence activation of these enzymes, suggesting that the primary physiological function of mitochondrial Ca 2+-transport is to be involved in this relay mechanism. This may also explain how in such circumstances rates of ATP production may be increased to meet the greater demand, but without any decreases in ATP ADP occurring.