PMID- 20624914
OWN - NLM
STAT- MEDLINE
DCOM- 20101004
LR  - 20220224
IS  - 1098-5549 (Electronic)
IS  - 0270-7306 (Print)
IS  - 0270-7306 (Linking)
VI  - 30
IP  - 18
DP  - 2010 Sep
TI  - Analysis of Leigh syndrome mutations in the yeast SURF1 homolog reveals a new 
      member of the cytochrome oxidase assembly factor family.
PG  - 4480-91
LID - 10.1128/MCB.00228-10 [doi]
AB  - Three missense SURF1 mutations identified in patients with Leigh syndrome (LS) 
      were evaluated in the yeast homolog Shy1 protein. Introduction of two of the 
      Leigh mutations, F(249)T and Y(344)D, in Shy1 failed to significantly attenuate 
      the function of Shy1 in cytochrome c oxidase (CcO) biogenesis as seen with the 
      human mutations. In contrast, a G(137)E substitution in Shy1 results in a 
      nonfunctional protein conferring a CcO deficiency. The G(137)E Shy1 mutant 
      phenocopied shy1Delta cells in impaired Cox1 hemylation and low mitochondrial 
      copper. A genetic screen for allele-specific suppressors of the G(137)E Shy1 
      mutant revealed Coa2, Cox10, and a novel factor designated Coa4. Coa2 and Cox10 
      are previously characterized CcO assembly factors. Coa4 is a twin CX(9)C motif 
      mitochondrial protein localized in the intermembrane space and associated with 
      the inner membrane. Cells lacking Coa4 are depressed in CcO activity but show no 
      impairment in Cox1 maturation or formation of the Shy1-stabilized Cox1 assembly 
      intermediate. To glean insights into the functional role of Coa4 in CcO 
      biogenesis, an unbiased suppressor screen of coa4Delta cells was conducted. 
      Respiratory function of coa4Delta cells was restored by the overexpression of 
      CYC1 encoding cytochrome c. Cyc1 is known to be important at an ill-defined step 
      in the assembly and/or stability of CcO. This new link to Coa4 may begin to 
      further elucidate the role of Cyc1 in CcO biogenesis.
FAU - Bestwick, Megan
AU  - Bestwick M
AD  - University of Utah Health Sciences Center, Department of Medicine, Salt Lake 
      City, Utah 84132, USA.
FAU - Jeong, Mi-Young
AU  - Jeong MY
FAU - Khalimonchuk, Oleh
AU  - Khalimonchuk O
FAU - Kim, Hyung
AU  - Kim H
FAU - Winge, Dennis R
AU  - Winge DR
LA  - eng
GR  - R01 ES003817/ES/NIEHS NIH HHS/United States
GR  - R37 ES003817/ES/NIEHS NIH HHS/United States
GR  - T32 DK007115/DK/NIDDK NIH HHS/United States
GR  - ES03817/ES/NIEHS NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
DEP - 20100712
PL  - United States
TA  - Mol Cell Biol
JT  - Molecular and cellular biology
JID - 8109087
RN  - 0 (Coa2 protein, S cerevisiae)
RN  - 0 (Membrane Proteins)
RN  - 0 (Mitochondrial Proteins)
RN  - 0 (Protein Subunits)
RN  - 0 (SHY1 protein, S cerevisiae)
RN  - 0 (Saccharomyces cerevisiae Proteins)
RN  - 0 (Surf-1 protein)
RN  - EC 1.9.3.1 (Electron Transport Complex IV)
SB  - IM
MH  - Amino Acid Sequence
MH  - Animals
MH  - Cell Respiration/physiology
MH  - *Electron Transport Complex IV/genetics/metabolism
MH  - Humans
MH  - Leigh Disease/*genetics
MH  - *Membrane Proteins/genetics/metabolism
MH  - *Mitochondrial Proteins/genetics/metabolism
MH  - Molecular Sequence Data
MH  - *Mutation, Missense
MH  - Protein Biosynthesis
MH  - Protein Subunits/genetics/metabolism
MH  - Saccharomyces cerevisiae/*genetics/metabolism
MH  - *Saccharomyces cerevisiae Proteins/genetics/metabolism
MH  - Sequence Alignment
PMC - PMC2937524
EDAT- 2010/07/14 06:00
MHDA- 2010/10/05 06:00
PMCR- 2011/03/01
CRDT- 2010/07/14 06:00
PHST- 2010/07/14 06:00 [entrez]
PHST- 2010/07/14 06:00 [pubmed]
PHST- 2010/10/05 06:00 [medline]
PHST- 2011/03/01 00:00 [pmc-release]
AID - MCB.00228-10 [pii]
AID - 0228-10 [pii]
AID - 10.1128/MCB.00228-10 [doi]
PST - ppublish
SO  - Mol Cell Biol. 2010 Sep;30(18):4480-91. doi: 10.1128/MCB.00228-10. Epub 2010 Jul 
      12.