Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Pivot Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Target Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Query: UMLS:C0004134 (
ataxia
)
15,886
document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)
Defects in mitochondrial cytochrome
c
oxidase or respiratory chain complex IV (CIV) assembly are a frequent cause of human mitochondrial disorders. Specifically, mutations in four conserved assembly factors impinging the biogenesis of the mitochondrion-encoded catalytic core subunit 2 (COX2) result in myopathies. These factors afford stability of newly synthesized COX2 (the dystonia-
ataxia
syndrome protein COX20), a protein with two transmembrane domains, and maturation of its copper center, Cu
A
(cardiomyopathy proteins
SCO1
, SCO2, and COA6). COX18 is an additional COX2 assembly factor that belongs to the Oxa1 family of membrane protein insertases. Here, we used a gene-editing approach to generate a human
COX18
knock-out HEK293T cell line that displays isolated complete CIV deficiency. We demonstrate that COX20 stabilizes COX2 during insertion of its N-proximal transmembrane domain, and subsequently, COX18 transiently interacts with COX2 to promote translocation across the inner membrane of the COX2 C-tail that contains the apo-Cu
A
site. The release of COX18 from this complex coincides with the binding of the
SCO1
-SCO2-COA6 copper metallation module to COX2-COX20 to finalize COX2 biogenesis. Therefore, COX18 is a new candidate when screening for mitochondrial disorders associated with isolated CIV deficiency.
...
PMID:Human mitochondrial cytochrome
c
oxidase assembly factor COX18 acts transiently as a membrane insertase within the subunit 2 maturation module. 2833 Aug 71
