PMID- 19295170
OWN - NLM
STAT- MEDLINE
DCOM- 20090625
LR  - 20201209
IS  - 0363-6143 (Print)
IS  - 0363-6143 (Linking)
VI  - 296
IP  - 5
DP  - 2009 May
TI  - Loss of function of Sco1 and its interaction with cytochrome c oxidase.
PG  - C1218-26
LID - 10.1152/ajpcell.00564.2008 [doi]
AB  - Sco1 and Sco2 are mitochondrial copper-binding proteins involved in the 
      biogenesis of the Cu(A) site in the cytochrome c oxidase (CcO) subunit Cox2 and 
      in the maintenance of cellular copper homeostasis. Human Surf1 is a CcO assembly 
      factor with an important but poorly characterized role in CcO biogenesis. Here, 
      we analyzed the impact on CcO assembly and tissue copper levels of a G132S 
      mutation in the juxtamembrane region of SCO1 metallochaperone associated with 
      early onset hypertrophic cardiomyopathy, encephalopathy, hypotonia, and 
      hepatopathy, assessed the total copper content of various SURF1 and 
      SCO2-deficient tissues, and investigated the possible physical association 
      between CcO and Sco1. The steady-state level of mutant Sco1 was severely 
      decreased in the muscle mitochondria of the SCO1 patient, indicating compromised 
      stability and thus loss of function of the protein. Unlike the wild-type variant, 
      residual mutant Sco1 appeared to migrate exclusively in the monomeric form on 
      blue native gels. Both the activity and content of CcO were reduced in the 
      patient's muscle to approximately 10-20% of control values. SCO1-deficient 
      mitochondria showed accumulation of two Cox2 subcomplexes, suggesting that Sco1 
      is very likely responsible for a different posttranslational aspect of Cox2 
      maturation than Sco2. Intriguingly, the various SURF1-deficient samples analyzed 
      showed a tissue-specific copper deficiency similar to that of SCO-deficient 
      samples, suggesting a role for Surf1 in copper homeostasis regulation. Finally, 
      both blue native immunoblot analysis and coimmunoprecipitation revealed that a 
      fraction of Sco1 physically associates with the CcO complex in human muscle 
      mitochondria, suggesting a possible direct relationship between CcO and the 
      regulation of cellular copper homeostasis.
FAU - Stiburek, Lukas
AU  - Stiburek L
AD  - Charles University, Prague 128 08, Czech Republic.
FAU - Vesela, Katerina
AU  - Vesela K
FAU - Hansikova, Hana
AU  - Hansikova H
FAU - Hulkova, Helena
AU  - Hulkova H
FAU - Zeman, Jiri
AU  - Zeman J
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20090318
PL  - United States
TA  - Am J Physiol Cell Physiol
JT  - American journal of physiology. Cell physiology
JID - 100901225
RN  - 0 (Carrier Proteins)
RN  - 0 (Membrane Proteins)
RN  - 0 (Mitochondrial Proteins)
RN  - 0 (Molecular Chaperones)
RN  - 0 (SCO1 protein, human)
RN  - 0 (SCO2 protein, human)
RN  - 0 (Surf-1 protein)
RN  - 789U1901C5 (Copper)
RN  - EC 1.9.3.- (cytochrome C oxidase subunit II)
RN  - EC 1.9.3.1 (Electron Transport Complex IV)
SB  - IM
MH  - Carrier Proteins/genetics/metabolism
MH  - Cell Line
MH  - Copper/deficiency/*metabolism
MH  - Electron Transport Complex IV/*metabolism
MH  - Female
MH  - Fetal Growth Retardation/genetics/*metabolism/pathology
MH  - Fibroblasts/enzymology/*pathology
MH  - Homeostasis/physiology
MH  - Humans
MH  - Infant
MH  - Kidney/cytology
MH  - Liver/enzymology/pathology
MH  - Membrane Proteins/genetics/*metabolism
MH  - Mitochondria/physiology
MH  - Mitochondrial Proteins/genetics/*metabolism
MH  - Molecular Chaperones
MH  - Myocytes, Cardiac/enzymology/pathology
MH  - Skin/cytology
EDAT- 2009/03/20 09:00
MHDA- 2009/06/26 09:00
CRDT- 2009/03/20 09:00
PHST- 2009/03/20 09:00 [entrez]
PHST- 2009/03/20 09:00 [pubmed]
PHST- 2009/06/26 09:00 [medline]
AID - 00564.2008 [pii]
AID - 10.1152/ajpcell.00564.2008 [doi]
PST - ppublish
SO  - Am J Physiol Cell Physiol. 2009 May;296(5):C1218-26. doi: 
      10.1152/ajpcell.00564.2008. Epub 2009 Mar 18.