The human mitochondrial Mrs2 protein functionally substitutes for its yeast homologue, a candidate magnesium transporter

We report here on the human MRS2 gene that encodes a protein, hsaMrs2p, the first molecularly characterized candidate for a magnesium transporter in m etazoa, The protein, like the yeast mitochondrial Mrs2 and Lpe10 proteins, contains two predicted transmembrane domains in its carboxyl-terminus, the first of which terminates with the conserved motif F/Y-G-M-N. These are typ ical features of the CorA family of magnesium transporters. Expression of h saMrs2p in mrs2-1 knock-out mutant yeast partly restores mitochondrial magn esium concentrations that are significantly reduced in this mutant. It also alleviates other defects of this mutant, which may be secondary to the red uction in magnesium concentrations. These findings suggest that hsaMrs2p an d yMrs2p are functional homologues, Like its yeast homologues, hsaMrs2p has been localized in mitochondria, The hsaMRS2 gene is located on chromosome 6 (6p22.1-p22.3) and is composed of II exons. A low level of the transcript is detected in various mouse tissues. (C) 2001 Academic Press.