Carnitine transport by organic cation transporters and systemic carnitine deficiency

The intracellular homeostasis is controlled by different membrane transport ers. Organic cation transporters function primarily in the elimination of c ationic drugs, endogenous amines, and other xenobiotics in tissues such as the kidney, intestine, and liver. Among these molecules, carnitine is an en dogenous amine which is an essential cofactor for mitochondrial beta -oxida tion. Recently, a new family of transporters, named OCT (organic cation tra nsporters) has been described. In this minireview, we present the recent kn owledge about OCT and focus on carnitine transport, more particularly by th e OCTN2. The importance of this sodium-dependent carnitine cotransporter, O CTN2, comes from various recently reported mutations in the gene which give rise to the primary systemic carnitine deficiency (SCD; OMIM 212140). The SCD is an autosomal recessive disorder of fatty acid oxidation characterize d by skeletal myopathy, progressive cardiomyopathy, hypoglycemia and hypera mmonemia. Most of the OCTN2 mutations identified in humans with SCD result in loss of carnitine transport function. Identifying these mutations will a llow an easy targeting of the SCD syndrome. The characteristics of the juve nile visceral steatosis (jvs) mouse, an animal model of SCD showing similar symptoms as humans having this genetic disorder, are also described. These mice have a mutation in the gene encoding the mouse carnitine transporter octn2. Although various OCTN carnitine transporters have been identified an d functionally characterized, their membrane localization and regulation ar e still unknown and must be investigated. This knowledge will also help in designing new drugs that regulate carnitine transport activity. (C) 2001 Ac ademic Press.