The Saccharomyces cerevisiae ATP22 Gene Codes for the Mitochondrial ATPase Subunit 6-Specific Translation Factor

Abstract

Mutations in the Saccharomyces cerevisiae ATP22 gene were previously shown to block assembly of the F 0 component of the mitochondrial proton-translocating ATPase. Further inquiries into the function of Atp22p have revealed that it is essential for translation of subunit 6 of the mitochondrial ATPase. The mutant phenotype can be partially rescued by the presence in the same cell of wild-type mitochondrial DNA and a r À deletion genome in which the 59-UTR, first exon, and first intron of COX1 are fused to the fourth codon of ATP6. The COX1/ATP6 gene is transcribed and processed to the mature mRNA by splicing of the COX1 intron from the precursor. The hybrid protein translated from the novel mRNA is proteolytically cleaved at the normal site between residues 10 and 11 of the subunit 6 precursor, causing the release of the polypeptide encoded by the COX1 exon. The ability of the r À suppressor genome to express subunit 6 in an atp22 null mutant constitutes strong evidence that translation of subunit 6 depends on the interaction of Atp22p with the 59-UTR of the ATP6 mRNA.

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

“…ATP22, which was previously shown to code for an Atp6p-specific translational activator (21), is a high copy suppressor of the Atp6p translation defect in F 1 mutants. This further substantiates the in vivo translation results and the ARG8 m expression data indicating that regulation by F 1 is exerted at the translational stage.…”

“…In earlier studies, the function of Atp22p was inferred from the phenotype of atp22 mutants, which are blocked in translation of Atp6p but not Atp8p (21). In view of this, the ability of ATP22 to partially suppress the arginine auxotrophy of ⌬atp12⌬arg8 double mutants with the mitochondrial ⌬atp8::ARG8 m allele was unexpected (Fig.…”

“…The yeast nuclear ATP22 gene codes for an Atp6p-specific translational activator (21). In the present study this gene was isolated based on its ability to suppress the arginine requirement of the ⌬atp12 ⌬arg8 double mutant with the ⌬atp6::ARG8 m mitochondrial allele.…”

Mechanisms of mitochondrial translational regulation

“…As mentioned earlier, Atp22 acts as an ATP6 mRNA-specific translational activator; however, ARG8 m expression from the ATP8 locus is slightly affected in a atp22 null mutant compared to wild type (10), suggesting that it could also play a still undefined nonessential role in Atp8 synthesis. Alternatively, Atp22 could indirectly affect ATP8 translation by altering the efficiency of the bicistronic ATP6/8 mRNA processing, as reported earlier (52). In a similar fashion, the product of the uncharacterized open-reading frame YJL147c could also play some additional role.…”

Investigation of yeast genes possibly involved in mtDNA stability using the nematode Caenorhabditis elegans

“…The mitochondrial genome, 16.6 kb in human and 85.8 kb in yeast, is predominantly linear in yeast but is circular in human (Burger et al, 2003;Legros et al, 2004;Williamson, 2002). Finally, heteroplasmy is very frequently observed for mtDNA mutations in human, whereas yeast cannot normally maintain stably heteroplasmy (Shoubridge, 1998;Zeng et al, 2007). Furthermore, because this yeast can grow robustly by fermentation in the absence of mtDNA, it loses its mitochondrial genome very rapidly upon inactivation of a large class of genes encoding mitochondrial proteins involved in almost all the mitochondrial biogenesis pathways (mitochondrial translation, adenosine triphosphate (ATP) synthesis, iron homeostasis, mitochondrial import, and morphology).…”