Structure/function relationships of mitochondrial protein carrier (SLC25A20) for carnitine/acylcarnitine: A review

The mitochondrial carnitine/acylcarnitine carrier (CAC) is a member of the mitochondrial carrier (MC) family. It facilitates the import of acylcarnitines into the mitochondrial matrix in exchange for carnitine, playing a crucial role in the carnitine shuttle, being essential for fatty acid oxidation and ATP production. This review summarizes three decades of progress in our research on the structural features of CAC. Although the crystallized structure of CAC has not yet been determined, several in vitro and in silico studies, many of which utilized the three-dimensional structures of the ADP/ATP carrier in both its cytosolic and matrix conformations, offers valuable insights for shed light on the molecular mechanism of substrate transport, supporting the hypothesis of a common single-binding centered-gated pore mechanism shared by all mitochondrial carriers. In addition, we discuss the transient dimerization of CAC and the formation of a supramolecular complex with a channeling function. Finally, the mechanistic analysis of CAC reported in this review could lay the basis for the development of new therapeutic strategies for patients with impaired CAC function.