A novel mitochondrial carrier protein Mme1 acts as a yeast mitochondrial magnesium exporter

Abstract The homeostasis of magnesium (Mg 2 + ), an abundant divalent cation indispensable for many biological processes including mitochondrial functions, is underexplored. Previously, two mitochondrial Mg 2 + importers, Mrs2 and Lpe10, were characterized for mitochondrial Mg 2 + uptake. We now show that mitochondrial Mg 2 + homeostasis is accurately controlled through the combined effects of previously known importers and a novel exporter, Mme1 (mitochondrial magnesium exporter 1). Mme1 belongs to the mitochondrial carrier family and was isolated for its mutation that is able to suppress the mrs2Δ respiration defect. Deletion of MME1 significantly increased steady-state mitochondrial Mg 2 + concentration, while overexpression decreased it. Measurements of Mg 2 + exit from proteoliposomes reconstituted with purified Mme1 provided definite evidence for Mme1 as an Mg 2 + exporter. Our studies identified, for the first time, a mitochondrial Mg 2 + exporter that works together with mitochondrial importers to ensure the precise control of mitochondrial Mg 2 + homeostasis.