Mss51p and Cox14p jointly regulate mitochondrial Cox1p expression in Saccharomyces cerevisiae

Abstract

Mutations in SURF1, the human homologue of yeast SHY1, are responsible for Leigh's syndrome, a neuropathy associated with cytochrome oxidase (COX) deficiency. Previous studies of the yeast model of this disease showed that mutant forms of Mss51p, a translational activator of COX1 mRNA, partially rescue the COX deficiency of shy1 mutants by restoring normal synthesis of the mitochondrially encoded Cox1p subunit of COX. Here we present evidence showing that Cox1p synthesis is reduced in most COX mutants but is restored to that of wild type by the same mss51 mutation that suppresses shy1 mutants. An important exception is a null mutation in COX14, which by itself or in combination with other COX mutations does not affect Cox1p synthesis. Cox14p and Mss51p are shown to interact with newly synthesized Cox1p and with each other. We propose that the interaction of Mss51p and Cox14p with Cox1p to form a transient Cox14p–Cox1p–Mss51p complex functions to downregulate Cox1p synthesis. The release of Mss51p from the complex occurs at a downstream step in the assembly pathway, probably catalyzed by Shy1p

F 1 -dependent translation of mitochondrially encoded Atp6p and Atp8p subunits of yeast ATP synthase

“…Activation of Atp6p translation by F 1 does not involve the CES mechanism proposed to regulate some chloroplast genes in Chlamydomonas (1, 2) and the mitochondrial COX1 gene in yeast (3). An essential feature of this mechanism is that a factor needed for translation of a specific mRNA also binds to the newly synthesized but unassembled protein product.…”

hCOA3 Stabilizes Cytochrome c Oxidase 1 (COX1) and Promotes Cytochrome c Oxidase Assembly in Human Mitochondria

“…Mss51, the central protein of a negative feedback translational regulatory system in yeast, has a dual function acting as a translational activator of COX1 mRNA and as a COX1 chaperone during the first steps of COX biogenesis (39). During and after synthesis, COX1 is bound to Mss51 in a complex stabilized by two small COX-specific chaperones, Cox14 (40) and Coa3 (37,38) and the mitochondrial Hsp70 chaperone (41). When COX1 pro-FIGURE 8. hCOA3 interacts with COX structural subunits and complex I.…”

Evidence for regulatory function of nucleus-encoded factors on mRNA stabilization and translation in the chloroplast

“…b 6 f complexes (27). In the yeast S. cerevisiae also, Pet111p is limiting for cox2 mRNA translation, but its overexpression increased accumulation of COX2p (28), presumably because the rate of COX2p synthesis is not limited by its assembly in cyt.-oxidase (29).…”