title: A heme-sensing mechanism in the translational regulation of mitochondrial cytochrome c oxidase biogenesis.
abstract: Heme plays fundamental roles as cofactor and signaling molecule in multiple pathways devoted to oxygen sensing and utilization in aerobic organisms. For cellular respiration, heme serves as a prosthetic group in electron transfer proteins and redox enzymes. Here we report that in the yeast Saccharomyces cerevisiae, a heme-sensing mechanism translationally controls the biogenesis of cytochrome c oxidase (COX), the terminal mitochondrial respiratory chain enzyme. We show that Mss51, a COX1 mRNA-specific translational activator and Cox1 chaperone, which coordinates Cox1 synthesis in mitoribosomes with its assembly in COX, is a heme-binding protein. Mss51 contains two heme regulatory motifs or Cys-Pro-X domains located in its N terminus. Using a combination of in vitro and in vivo approaches, we have demonstrated that these motifs are important for heme binding and efficient performance of Mss51 functions. We conclude that heme sensing by Mss51 regulates COX biogenesis and aerobic energy production.
authors.affiliation: Department of Neurology, University of Miami Miller School of Medicine, Miami, FL 33136, USA.
authors.forename: Iliana C
authors.initials: IC
authors.lastname: Soto
authors.forename: Flavia
authors.initials: F
authors.lastname: Fontanesi
authors.forename: Richard S
authors.initials: RS
authors.lastname: Myers
authors.forename: Patrice
authors.initials: P
authors.lastname: Hamel
authors.forename: Antoni
authors.initials: A
authors.lastname: Barrientos
mesh_terms: D020816:Amino Acid Motifs; D000595:Amino Acid Sequence; D003576:Electron Transport Complex IV / Q000235:genetics / Q000378:metabolism*; D006418:Heme / Q000378:metabolism*; D007700:Kinetics; D008928:Mitochondria / Q000201:enzymology*; D063269:Mitochondrial Turnover; D008969:Molecular Sequence Data; D009154:Mutation; D011485:Protein Binding; D011499:Protein Processing, Post-Translational; D011994:Recombinant Proteins / Q000096:biosynthesis / Q000737:chemistry / Q000235:genetics; D012441:Saccharomyces cerevisiae / Q000378:metabolism; D029701:Saccharomyces cerevisiae Proteins / Q000235:genetics / Q000378:metabolism*; D016415:Sequence Alignment; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism
chemical_list: C519191:Mss51 protein, S cerevisiae; D011994:Recombinant Proteins; D029701:Saccharomyces cerevisiae Proteins; D014157:Transcription Factors; D006418:Heme; C526453:Cox1 protein, S cerevisiae; D003576:Electron Transport Complex IV