title: Yeast cells lacking the mitochondrial gene encoding the ATP synthase subunit 6 exhibit a selective loss of complex IV and unusual mitochondrial morphology.
abstract: Atp6p is an essential subunit of the ATP synthase proton translocating domain, which is encoded by the mitochondrial DNA (mtDNA) in yeast. We have replaced the coding sequence of Atp6p gene with the non-respiratory genetic marker ARG8m. Due to the presence of ARG8m, accumulation of rho-/rho0 petites issued from large deletions in mtDNA could be restricted to 20-30% by growing the atp6 mutant in media lacking arginine. This moderate mtDNA instability created favorable conditions to investigate the consequences of a specific lack in Atp6p. Interestingly, in addition to the expected loss of ATP synthase activity, the cytochrome c oxidase respiratory enzyme steady-state level was found to be extremely low (<5%) in the atp6 mutant. We show that the cytochrome c oxidase-poor accumulation was caused by a failure in the synthesis of one of its mtDNA-encoded subunits, Cox1p, indicating that, in yeast mitochondria, Cox1p synthesis is a key target for cytochrome c oxidase abundance regulation in relation to the ATP synthase activity. We provide direct evidence showing that in the absence of Atp6p the remaining subunits of the ATP synthase can still assemble. Mitochondrial cristae were detected in the atp6 mutant, showing that neither Atp6p nor the ATP synthase activity is critical for their formation. However, the atp6 mutant exhibited unusual mitochondrial structure and distribution anomalies, presumably caused by a strong delay in inner membrane fusion.
authors.affiliation: Institut de Biochimie et Génétique Cellulaires, Université Victor Segalen, 1 Rue Camille Saint-Saëns, 33077 Bordeaux cedex, France.
authors.forename: Malgorzata
authors.initials: M
authors.lastname: Rak
authors.forename: Emmanuel
authors.initials: E
authors.lastname: Tetaud
authors.forename: François
authors.initials: F
authors.lastname: Godard
authors.forename: Isabelle
authors.initials: I
authors.lastname: Sagot
authors.forename: Bénédicte
authors.initials: B
authors.lastname: Salin
authors.forename: Stéphane
authors.initials: S
authors.lastname: Duvezin-Caubet
authors.forename: Piotr P
authors.initials: PP
authors.lastname: Slonimski
authors.forename: Joanna
authors.initials: J
authors.lastname: Rytka
authors.forename: Jean-Paul
authors.initials: JP
authors.lastname: di Rago
mesh_terms: D000255:Adenosine Triphosphate / Q000378:metabolism; D048430:Cell Shape; D045304:Cytochromes c / Q000378:metabolism; D004272:DNA, Mitochondrial / Q000235:genetics; D017353:Gene Deletion; D015966:Gene Expression Regulation, Fungal; D050259:Genes, Mitochondrial / Q000235:genetics*; D005838:Genotype; D006868:Hydrolysis; D008854:Microscopy, Electron; D008928:Mitochondria / Q000201:enzymology* / Q000235:genetics; D025261:Mitochondrial Proton-Translocating ATPases / Q000235:genetics / Q000378:metabolism*; D010088:Oxidoreductases / Q000378:metabolism; D010100:Oxygen / Q000378:metabolism; D014176:Protein Biosynthesis / Q000235:genetics; D012441:Saccharomyces cerevisiae / Q000166:cytology* / Q000201:enzymology* / Q000235:genetics; D000637:Transaminases / Q000235:genetics / Q000378:metabolism; D014158:Transcription, Genetic / Q000235:genetics
chemical_list: D004272:DNA, Mitochondrial; D000255:Adenosine Triphosphate; D045304:Cytochromes c; D010088:Oxidoreductases; D000637:Transaminases; C018731:acetylornithine transaminase; C412204:ATP synthase subunit 6; D025261:Mitochondrial Proton-Translocating ATPases; D010100:Oxygen