title: Redox and reactive oxygen species regulation of mitochondrial cytochrome C oxidase biogenesis.
abstract: CONCLUSIONS
  Cytochrome c oxidase (COX), the last enzyme of the mitochondrial respiratory chain, is the major oxygen consumer enzyme in the cell. COX biogenesis involves several redox-regulated steps. The process is highly regulated to prevent the formation of pro-oxidant intermediates.
  
  
  BACKGROUND
  Regulation of COX assembly involves several reactive oxygen species and redox-regulated steps. These include: (i) Intricate redox-controlled machineries coordinate the expression of COX isoenzymes depending on the environmental oxygen concentration. (ii) COX is a heme A-copper metalloenzyme. COX copper metallation involves the copper chaperone Cox17 and several other recently described cysteine-rich proteins, which are oxidatively folded in the mitochondrial intermembrane space. Copper transfer to COX subunits 1 and 2 requires concomitant transfer of redox power. (iii) To avoid the accumulation of reactive assembly intermediates, COX is regulated at the translational level to minimize synthesis of the heme A-containing Cox1 subunit when assembly is impaired.
  
  
  RESULTS
  An increasing number of regulatory pathways converge to facilitate efficient COX assembly, thus preventing oxidative stress.
  
  
  CONCLUSIONS
  Here we will review on the redox-regulated COX biogenesis steps and will discuss their physiological relevance. Forthcoming insights into the precise regulation of mitochondrial COX biogenesis in normal and stress conditions will likely open future perspectives for understanding mitochondrial redox regulation and prevention of oxidative stress.
authors.affiliation: 1 Department of Neurology, University of Miami Miller School of Medicine , Miami, Florida.
authors.forename: Myriam
authors.initials: M
authors.lastname: Bourens
authors.forename: Flavia
authors.initials: F
authors.lastname: Fontanesi
authors.forename: Iliana C
authors.initials: IC
authors.lastname: Soto
authors.forename: Jingjing
authors.initials: J
authors.lastname: Liu
authors.forename: Antoni
authors.initials: A
authors.lastname: Barrientos
mesh_terms: D000818:Animals; D003576:Electron Transport Complex IV / Q000096:biosynthesis* / Q000235:genetics*; D006801:Humans; D008928:Mitochondria / Q000201:enzymology* / Q000378:metabolism; D010084:Oxidation-Reduction; D017382:Reactive Oxygen Species / Q000378:metabolism*
chemical_list: D017382:Reactive Oxygen Species; D003576:Electron Transport Complex IV