title: Shy1p is necessary for full expression of mitochondrial COX1 in the yeast model of Leigh's syndrome.
abstract: SHY1 codes for a mitochondrial protein required for full expression of cytochrome oxidase (COX) in Saccharomyces cerevisiae. Mutations in the homologous human gene (SURF1) have been reported to cause Leigh's syndrome, a neurological disease associated with COX deficiency. The function of Shy1p/Surf1p is poorly understood. Here we have characterized revertants of shy1 null mutants carrying extragenic nuclear suppressor mutations. The steady-state levels of COX in the revertants is increased by a factor of 4-5, accounting for their ability to respire and grow on non-fermentable carbon sources at nearly wild-type rates. The suppressor mutations are in MSS51, a gene previously implicated in processing and translation of the COX1 transcript for subunit 1 (Cox1) of COX. The function of Shy1p and the mechanism of suppression of shy1 mutants were examined by comparing the rates of synthesis and turnover of the mitochondrial translation products in wild-type, mutant and revertant cells. We propose that Shy1p promotes the formation of an assembly intermediate in which Cox1 is one of the partners.
authors.affiliation: Department of Biological Sciences, Columbia University, New York, NY 10027, USA.
authors.forename: Antoni
authors.initials: A
authors.lastname: Barrientos
authors.forename: Daniel
authors.initials: D
authors.lastname: Korr
authors.forename: Alexander
authors.initials: A
authors.lastname: Tzagoloff
mesh_terms: D001483:Base Sequence; D004271:DNA, Fungal / Q000235:genetics; D003576:Electron Transport Complex IV / Q000235:genetics*; D015870:Gene Expression; D006801:Humans; D007527:Isoenzymes; D007888:Leigh Disease / Q000235:genetics* / Q000378:metabolism*; D008565:Membrane Proteins / Q000235:genetics* / Q000378:metabolism*; D008928:Mitochondria / Q000201:enzymology; D024101:Mitochondrial Proteins; D008954:Models, Biological; D009154:Mutation; D010085:Oxidative Phosphorylation; D011451:Prostaglandin-Endoperoxide Synthases; D014176:Protein Biosynthesis; D011506:Proteins / Q000235:genetics / Q000378:metabolism; D012441:Saccharomyces cerevisiae / Q000235:genetics* / Q000378:metabolism*; D029701:Saccharomyces cerevisiae Proteins / Q000235:genetics* / Q000378:metabolism*; D013489:Suppression, Genetic
chemical_list: D004271:DNA, Fungal; D007527:Isoenzymes; D008565:Membrane Proteins; D024101:Mitochondrial Proteins; D011506:Proteins; C106291:SHY1 protein, S cerevisiae; D029701:Saccharomyces cerevisiae Proteins; C092928:Surf-1 protein; D011451:Prostaglandin-Endoperoxide Synthases; D003576:Electron Transport Complex IV