PMID- 10486321
OWN - NLM
STAT- MEDLINE
DCOM- 20001002
LR  - 20200824
IS  - 0002-9297 (Print)
IS  - 0002-9297 (Linking)
VI  - 65
IP  - 4
DP  - 1999 Oct
TI  - A missense mutation of cytochrome oxidase subunit II causes defective assembly
      and myopathy.
PG  - 1030-9
AB  - We report the first missense mutation in the mtDNA gene for subunit II of
      cytochrome c oxidase (COX). The mutation was identified in a 14-year-old boy with
      a proximal myopathy and lactic acidosis. Muscle histochemistry and mitochondrial 
      respiratory-chain enzymology demonstrated a marked reduction in COX activity.
      Immunohistochemistry and immunoblot analyses with COX subunit-specific monoclonal
      antibodies showed a pattern suggestive of a primary mtDNA defect, most likely
      involving CO II, for COX subunit II (COX II). mtDNA-sequence analysis
      demonstrated a novel heteroplasmic T-->A transversion at nucleotide position
      7,671 in CO II. This mutation changes a methionine to a lysine residue in the
      middle of the first N-terminal membrane-spanning region of COX II. The immunoblot
      studies demonstrated a severe reduction in cross-reactivity, not only for COX II 
      but also for the mtDNA-encoded subunit COX III and for nuclear-encoded subunits
      Vb, VIa, VIb, and VIc. Steady-state levels of the mtDNA-encoded subunit COX I
      showed a mild reduction, but spectrophotometric analysis revealed a dramatic
      decrease in COX I-associated heme a3 levels. These observations suggest that, in 
      the COX protein, a structural association of COX II with COX I is necessary to
      stabilize the binding of heme a3 to COX I.
FAU - Rahman, S
AU  - Rahman S
AD  - University Department of Clinical Neurosciences, Royal Free and University
      College Medical School, Rowland Hill Street, London, United Kingdom.
FAU - Taanman, J W
AU  - Taanman JW
FAU - Cooper, J M
AU  - Cooper JM
FAU - Nelson, I
AU  - Nelson I
FAU - Hargreaves, I
AU  - Hargreaves I
FAU - Meunier, B
AU  - Meunier B
FAU - Hanna, M G
AU  - Hanna MG
FAU - Garcia, J J
AU  - Garcia JJ
FAU - Capaldi, R A
AU  - Capaldi RA
FAU - Lake, B D
AU  - Lake BD
FAU - Leonard, J V
AU  - Leonard JV
FAU - Schapira, A H
AU  - Schapira AH
LA  - eng
GR  - Wellcome Trust/United Kingdom
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Am J Hum Genet
JT  - American journal of human genetics
JID - 0370475
RN  - 0 (DNA, Mitochondrial)
RN  - 0 (Holoenzymes)
RN  - 18535-39-2 (heme a)
RN  - 42VZT0U6YR (Heme)
RN  - EC 1.9.3.- (cytochrome C oxidase subunit II)
RN  - EC 1.9.3.1 (Electron Transport Complex IV)
SB  - IM
MH  - Acidosis, Lactic/enzymology/genetics/metabolism/pathology
MH  - Adolescent
MH  - Amino Acid Sequence
MH  - Amino Acid Substitution/genetics
MH  - Base Sequence
MH  - Blotting, Western
MH  - Cell Nucleus/enzymology
MH  - Cell Respiration
MH  - Cells, Cultured
MH  - *Cytochrome-c Oxidase Deficiency
MH  - DNA, Mitochondrial/*genetics
MH  - Electron Transport Complex IV/*chemistry/genetics/metabolism
MH  - Enzyme Stability
MH  - Heme/*analogs & derivatives/metabolism
MH  - Holoenzymes/chemistry/deficiency/genetics/metabolism
MH  - Humans
MH  - Immunohistochemistry
MH  - Male
MH  - Mitochondria/enzymology/genetics/metabolism/pathology
MH  - Models, Molecular
MH  - Molecular Sequence Data
MH  - Muscles/enzymology/metabolism/pathology
MH  - Muscular Diseases/enzymology/*genetics/metabolism/pathology
MH  - Mutation, Missense/*genetics
MH  - Photolysis
MH  - Polarography
MH  - Protein Structure, Quaternary
MH  - Sequence Alignment
PMC - PMC1288235
EDAT- 1999/09/16 09:00
MHDA- 2000/10/07 11:01
CRDT- 1999/09/16 09:00
PHST- 1999/09/16 09:00 [pubmed]
PHST- 2000/10/07 11:01 [medline]
PHST- 1999/09/16 09:00 [entrez]
AID - S0002-9297(07)62605-6 [pii]
AID - 10.1086/302590 [doi]
PST - ppublish
SO  - Am J Hum Genet. 1999 Oct;65(4):1030-9. doi: 10.1086/302590.