Acylglycerol kinase: mitochondrial protein transport meets lipid biosynthesis

Trends Cell Biol.          online article

Mitochondrial carrier proteins  transports various metabolites across the inner membrane. The biogenesis of carrier proteins involves several steps. Precursor of carrier proteins are synthesized on cytosolic ribosomes and are guided by molecular chaperones to receptors of the translocase of the outer mitochondrial membrane (TOM complex). After the precursors passed the outer membrane via the TOM channel small TIM chaperones of the intermembrane space transfer them to the carrier translocase (TIM22 complex) for insertion into the inner membrane. Recently, the acylglycerol kinase (AGK) was identified as novel subunit of the TIM22 complex.  Mutations of AGK have been found in patients suffering the Sengers syndrome. Reduced levels of AGK impairs TIM22-dependent protein import. Previously, a role of AGK in lipid metabolism was described. The enzyme phosphorylates monoacylglycerol and diacylglycerol to produce lsyophosphatidic acid and phosphatidic acid. However, the kinase activity of AGK is not required for the import of carrier proteins. Thus, AGK provide a novel link between lipid homeostasis and protein import into mitochondria.