OVEREXPRESSION OF A NOVEL MEMBER OF THE MITOCHONDRIAL CARRIER FAMILY RESCUES DEFECTS IN BOTH DNA AND RNA-METABOLISM IN YEAST MITOCHONDRIA

The PIF1 and MRS2 gene products have previously been shown to be essen tial for mitochondrial DNA maintenance at elevated temperatures and mi tochondrial group II intron splicing, respectively, in the yeast Sacch aromyces cerevisiae. A multicopy suppressor capable of rescuing the re spiratory deficient phenotype associated with null alleles of either g ene has been isolated. This suppressor is a nuclear gene that was call ed RIM2/MRS12. The RIM2/MRS12 gene encodes a predicted protein of 377 amino acids that is essential for mitochondrial DNA metabolism and pro per cell growth. Inactivation of this gene causes the total loss of mi tochondrial DNA and, compared to wild-type rho degrees controls, a slo w-growth phenotype on media containing glucose. Analysis of the RIM2/M RS12 protein sequence suggests that RIM2/MRS12 encodes a novel member of the mitochondrial carrier family. In particular, a typical triplica te structure, where each repeat consists of two putative transmembrane segments separated by a hydrophilic loop, can be deduced from amino a cid sequence comparisons and the hydropathy profile of RIM2/MRS12. Ant ibodies directed against the aminoterminus of RIM2/MRS12 detect this p rotein in mitochondria. The function of the RIM2/MRS12 protein and the substrates it might transport are discussed.