Dual functions of Mss51 couple synthesis of Cox1 to assembly of cytochrome c oxidase in Saccharomyces cerevisiae mitochondria.
Functional interactions of the translational activator Mss51 with both the mitochondrially encoded COX1 mRNA 5'-untranslated region and with newly synthesized unassembled Cox1 protein suggest that it has a key role in coupling Cox1 synthesis with assembly of cytochrome c oxidase. Mss51 is present at levels that are near rate limiting for expression of a reporter gene inserted at COX1 in mitochondrial DNA, and a substantial fraction of Mss51 is associated with Cox1 protein in assembly intermediates. Thus, sequestration of Mss51 in assembly intermediates could limit Cox1 synthesis in wild type, and account for the reduced Cox1 synthesis caused by most yeast mutations that block assembly. Mss51 does not stably interact with newly synthesized Cox1 in a mutant lacking Cox14, suggesting that the failure of nuclear cox14 mutants to decrease Cox1 synthesis, despite their inability to assemble cytochrome c oxidase, is due to a failure to sequester Mss51. The physical interaction between Mss51 and Cox14 is dependent upon Cox1 synthesis, indicating dynamic assembly of early cytochrome c oxidase intermediates nucleated by Cox1. Regulation of COX1 mRNA translation by Mss51 seems to be an example of a homeostatic mechanism in which a positive effector of gene expression interacts with the product it regulates in a posttranslational assembly process.
Perez-Martinez
Xochitl
X
Departamento de Bioquímica, Instituto de Fisiología Celular, Universidad Nacional Autónoma de México, México D.F. 04510, México.
Butler
Christine A
CA
Shingu-Vazquez
Miguel
M
Fox
Thomas D
TD
D020121:5' Untranslated Regions; D003576:Electron Transport Complex IV / Q000096:biosynthesis* / Q000235:genetics; D015966:Gene Expression Regulation, Fungal / Q000502:physiology*; D017930:Genes, Reporter; D005813:Genes, Synthetic; D006706:Homeostasis; D008565:Membrane Proteins / Q000502:physiology; D008928:Mitochondria / Q000201:enzymology*; D024101:Mitochondrial Proteins / Q000502:physiology; D014176:Protein Biosynthesis / Q000502:physiology; D025941:Protein Interaction Mapping; D011499:Protein Processing, Post-Translational / Q000502:physiology; D021122:Protein Subunits; D012331:RNA, Fungal / Q000235:genetics / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D011993:Recombinant Fusion Proteins / Q000502:physiology; D012441:Saccharomyces cerevisiae / Q000235:genetics / Q000378:metabolism*; D029701:Saccharomyces cerevisiae Proteins / Q000096:biosynthesis* / Q000235:genetics / Q000502:physiology*; D014157:Transcription Factors / Q000235:genetics / Q000502:physiology*
D020121:5' Untranslated Regions; C094357:COX14 protein, S cerevisiae; D008565:Membrane Proteins; D024101:Mitochondrial Proteins; C519191:Mss51 protein, S cerevisiae; D021122:Protein Subunits; D012331:RNA, Fungal; D012333:RNA, Messenger; D011993:Recombinant Fusion Proteins; D029701:Saccharomyces cerevisiae Proteins; D014157:Transcription Factors; C526453:Cox1 protein, S cerevisiae; D003576:Electron Transport Complex IV