PMID- 17430883
OWN - NLM
STAT- MEDLINE
DCOM- 20070925
LR  - 20210209
IS  - 0021-9258 (Print)
IS  - 0021-9258 (Linking)
VI  - 282
IP  - 24
DP  - 2007 Jun 15
TI  - Evidence for a pro-oxidant intermediate in the assembly of cytochrome oxidase.
PG  - 17442-9
AB  - 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 Cu(A) and Cu(B) sites of CcO, respectively. 
      The respective wild-type genes suppress the peroxide sensitivities of sco1Delta 
      and cox11Delta 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 sco1Delta cells. Thus, a disconnect exists between the respiratory 
      capacity of cells and hydrogen peroxide sensitivity. Hydrogen peroxide 
      sensitivity of sco1Delta and cox11Delta 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.
FAU - Khalimonchuk, Oleh
AU  - Khalimonchuk O
AD  - University of Utah Health Sciences Center, Department of Medicine, Salt Lake 
      City, Utah 84132, USA.
FAU - Bird, Amanda
AU  - Bird A
FAU - Winge, Dennis R
AU  - Winge DR
LA  - eng
GR  - ES03817/ES/NIEHS NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
DEP - 20070412
PL  - United States
TA  - J Biol Chem
JT  - The Journal of biological chemistry
JID - 2985121R
RN  - 0 (COX11 protein, S cerevisiae)
RN  - 0 (Membrane Proteins)
RN  - 0 (Mitochondrial Proteins)
RN  - 0 (Oxidants)
RN  - 0 (Protein Subunits)
RN  - 0 (SCO1 protein, S cerevisiae)
RN  - 0 (Saccharomyces cerevisiae Proteins)
RN  - 18535-39-2 (heme a)
RN  - 42VZT0U6YR (Heme)
RN  - BBX060AN9V (Hydrogen Peroxide)
RN  - EC 1.9.3.1 (Electron Transport Complex IV)
RN  - EC 3.6.1.- (Adenosine Triphosphatases)
RN  - EC 3.6.1.- (Afg1 protein, S cerevisiae)
SB  - IM
MH  - Adenosine Triphosphatases/genetics/metabolism
MH  - Electron Transport Complex IV/chemistry/genetics/*metabolism
MH  - Heme/analogs & derivatives/chemistry/metabolism
MH  - Humans
MH  - Hydrogen Peroxide/*metabolism/pharmacology
MH  - Membrane Proteins/genetics/*metabolism
MH  - Mitochondria/metabolism
MH  - Mitochondrial Proteins/genetics/metabolism
MH  - Models, Molecular
MH  - Oxidants/*metabolism/pharmacology
MH  - Protein Structure, Tertiary
MH  - Protein Subunits/genetics/metabolism
MH  - Saccharomyces cerevisiae/drug effects/*metabolism
MH  - Saccharomyces cerevisiae Proteins/genetics/*metabolism
EDAT- 2007/04/14 09:00
MHDA- 2007/09/26 09:00
CRDT- 2007/04/14 09:00
PHST- 2007/04/14 09:00 [pubmed]
PHST- 2007/09/26 09:00 [medline]
PHST- 2007/04/14 09:00 [entrez]
AID - S0021-9258(20)69046-9 [pii]
AID - 10.1074/jbc.M702379200 [doi]
PST - ppublish
SO  - J Biol Chem. 2007 Jun 15;282(24):17442-9. doi: 10.1074/jbc.M702379200. Epub 2007 
      Apr 12.