LEU5 encodes a mitochondrial inner membrane protein that is involved in the transport of coenzyme A (CoA) to the mitochondrial matrix (2). It was originally thought that LEU5 encoded the minor isozyme of isopropylmalate synthase (1), but further analysis showed that Leu5p was not directly involved in leucine biosynthesis and was instead similar to mitochondrial carrier proteins (3, 4, and 2). Leu5p has sequence features characteristic of the mitochondrial carrier family: it lacks a typical N-terminal targeting sequence for mitochondrial matrix localization, and exhibits a tripartite structure with three repetitive domains, each comprised of two transmembrane regions and a carrier signature motif (4 and 2 and references therein).

Mutants lacking Leu5p activity grow poorly on non-fermentable carbon sources, such as glycerol, and exhibit a 15-fold decrease in mitochondrial CoA levels compared to wild-type cells (3, 2). A leu4 leu5 double mutant is synthetically auxotrophic for leucine (1). Leu5p has sequence similarity to S. pombe, bovine, and human proteins; expression of the human homolog SLC25A16 (OMIM), an autoantigen linked to Graves disease (OMIM), is able to rescue leu5 null cells (2 and references therein).

Last updated: 2006-08-10