Mitochondrial Ca2+ transport and the role of intramitochondrial Ca2+ in the regulation of energy metabolism.

The mitochondrial inner membrane of all mammalian tissues, including brain tissues, has specific active transport systems for the uptake and egress of Ca2+. The primary role of this transport system is to relay changes in cytosolic [Ca2+], which stimulates energy-requiring processes in the cytosol (e.g. secretion), into the mitochondrial matrix where it stimulates several key steps in energy production. Thus using the same second-messenger molecule, the latter events allow energetic homeostasis to be maintained under conditions of cell stimulation. This appears to be brought about by a co-ordinated enhancement of steps throughout the pathways of oxidative phosphorylation, including substrate supply to the respiratory chain by dehydrogenase activation, activation of the respiratory chain itself by a mechanism which appears to involve changes in the matrix volume, and also possibly activation of the ATP synthetase where the release of a specific inhibitory subunit has been proposed.