Mitochondrial Uptake and Accumulation of Vitamin C: What Can We Learn from Cell Culture Studies?

Significance: The mitochondrial fraction of l-ascorbic acid (AA) is of critical importance for the regulation of the redox status of these organelles and for cell survival. Recent Advances: Most cell types take up AA by the high-affinity sodium-dependent vitamin C transporter 2 (SVCT2) sensitive to inhibition by dehydroascorbic acid (DHA). DHA can also be taken up by glucose transporters (GLUTs) and then reduced back to AA. DHA concentrations, normally very low in biological fluids, may only become significant next to superoxide-releasing cells. Very little is known about the mechanisms mediating the mitochondrial transport of the vitamin. Critical Issues: Information on AA transport is largely derived from studies using cultured cells and is therefore conditioned by possible cell culture effects as overexpression of SVCT2 in the plasma membrane and mitochondria. Mitochondrial SVCT2 is susceptible to inhibition by DHA and transports AA with a low affinity as a consequence of the restrictive ionic conditions. In some cells, however, high-affinity mitochondrial transport of AA is observed. Mitochondrial uptake of DHA may take place through GLUTs, an event followed by its prompt reduction to AA in the matrix. Intracellular levels of DHA are, however, normally very low. Future Directions: We need to establish, or rule out, the role and significance of mitochondrial SVCT2 in vivo. The key question for mitochondrial DHA transport is instead related to its very low intracellular concentrations.