The mitochondrial transporter family SLC25: identification, properties and physiopathology.

SLC25 is a large family of nuclear-encoded transporters embedded in the inner mitochondrial membrane and in a few cases other organelle membranes. The members of this superfamily are widespread in eukaryotes and involved in numerous metabolic pathways and cell functions. They can be easily recognized by their striking sequence features, i.e., a tripartite structure, six transmembrane α-helices and a 3-fold repeated signature motifs. SLC25 members vary greatly in the nature and size of their transported substrates, modes of transport (i.e., uniport, symport or antiport) and driving forces, although the molecular mechanism of substrate translocation may be basically the same. Based on substrate specificity, 24 subfamilies, well conserved throughout evolution, have been functionally characterized mainly by transport assays upon heterologous gene expression, purification and reconstitution into liposomes. Several other SLC25 family members remain to be characterized. In recent years mutations in the SLC25 genes have been shown to be responsible for 11 diseases, highlighting the important role of SLC25 in metabolism.