Characterization of the Saccharomyces cerevisiae gene MGP1, a novel member of the ras gene superfamily that functions in the mitochondrial biogenesis

Abstract

Mutations in tlie Saccharomyces cerevisiae gene MSG1 cause pleiotropic respiratory deficiencies, as shown by complete loss of spectral absorption of cytochrome b and 3/83 from mitochondrial membranes. Pleiotropic effects of msg1 mutations were evident in mitochondrial biogenesis, such that one mitochondrial gene product, apocytochrome b was synthesized but did not assemble into holoenzyme, whereas other mitochondrial gene products, subunits 1, 2, and 3 of cytochrome oxidase, accumulated at significantly reduced levels. These data suggest msg7 mutations block assembly of mitochondrial respiratory enzyme complexes. The nuclear gene MGP1 was identified based on its ability to restore respiratory competence to strains with msg1 mutations. The MGP1 sequence codes for a protein, Mgp1p, of 526 residues in which the amino terminal sequence is typical of mitochondrial targeting peptides. A190 residue region of Mgp1p shares approximately 30% identity with any member of the large family of p21''as.related proteins. MGP1 did not cause respiratory deficiency, and MGP1 is not genetically linl<ed to MSG1. Therefore, MGP1 is an extragenic suppressor oimsgl mutations when present in multiple copies. The mutations mgp1A281-289 and mgplSer523 thought to affect nucleotide binding and post-translationai modification, respectively, inactivate the suppressor function oiMGPI assayed in vivo. These data suggest MGP1 functions in mitochondrial biogenesis using a biochemical mechanism similar to that of p21''as and related proteins.