Evidence for a pro-oxidant intermediate in the assembly of cytochrome oxidase

Oleh Khalimonchuk, Amanda Bird, Dennis R. Winge

Research output: Contribution to journalArticle

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Abstract

The hydrogen peroxide sensitivity of cells lacking two proteins, Sco1 and Cox11, important in the assembly of cytochrome c oxidase (CcO), is shown to arise from the transient accumulation of a pro-oxidant heme A-Cox1 stalled intermediate. The peroxide sensitivity of these cells is abrogated by a reduction in either Cox1 expression or heme A formation but exacerbated by either enhanced Cox1 expression or heme A production arising from overexpression of COX15. Sco1 and Cox11 are implicated in the formation of the CuA and CuB sites of CcO, respectively. The respective wild-type genes suppress the peroxide sensitivities of sco1Δ and cox11Δ cells, but no cross-complementation is seen with noncognate genes. Copper-binding mutant alleles of Sco1 and Cox11 that are nonfunctional in promoting the assembly of CcO are functional in suppressing the peroxide sensitivity of their respective null mutants. Likewise, human Sco1 that is nonfunctional in yeast CcO assembly is able to suppress the peroxide sensitivity of yeast sco1Δ cells. Thus, a disconnect exists between the respiratory capacity of cells and hydrogen peroxide sensitivity. Hydrogen peroxide sensitivity of sco1Δ and cox11Δ cells is abrogated by overexpression of a novel mitochondrial ATPase Afg1 that promotes the degradation of CcO mitochondrially encoded subunits. Studies on the hydrogen peroxide sensitivity in CcO assembly mutants reveal new aspects of the CcO assembly process.

Original languageEnglish (US)
Pages (from-to)17442-17449
Number of pages8
JournalJournal of Biological Chemistry
Volume282
Issue number24
DOIs
StatePublished - Jun 15 2007

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Electron Transport Complex IV
Reactive Oxygen Species
Peroxides
Hydrogen Peroxide
Heme
Yeast
Genes
Yeasts
Adenosine Triphosphatases
Copper
Alleles
Degradation
Proteins

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

Cite this

Evidence for a pro-oxidant intermediate in the assembly of cytochrome oxidase. / Khalimonchuk, Oleh; Bird, Amanda; Winge, Dennis R.

In: Journal of Biological Chemistry, Vol. 282, No. 24, 15.06.2007, p. 17442-17449.

Research output: Contribution to journalArticle

Khalimonchuk, Oleh ; Bird, Amanda ; Winge, Dennis R. / Evidence for a pro-oxidant intermediate in the assembly of cytochrome oxidase. In: Journal of Biological Chemistry. 2007 ; Vol. 282, No. 24. pp. 17442-17449.
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