Ascorbic acid is an endogenous cytosolic inhibitor of ATP-supported rat liver mitochondrial calcium transport.

ATP-supported but not Site I or Site II respiratory chain-linked 45Ca2+ transport into isolated rat liver mitochondria is profoundly inhibited by a small molecule present in the cytosolic fraction. This inhibitor was purified and shown to be identical with ascorbic acid in a number of chemical properties, cytosolic abundance, susceptibility to ascorbate oxidase, and to agents that otherwise block the effect of authentic ascorbic acid. Experiments with a variety of free radical scavengers and glutathione indicated that ascorbate inhibition of calcium transport is mediated through a 1-electron-free radical mechanism rather than a conventional 2-electron reaction. Calcium transport mechanisms may, therefore, be a target in the pathophysiology of disease processes that influence the intracellular ratios and levels of ascorbate and physiological radical scavengers.