Mitochondrial respiratory complex I can be inhibited via bypassing the ubiquinone-accessing tunnel.
complex I
inhibitor
mitochondria
proteoliposomes
respiratory enzymes
ubiquinone
Journal
FEBS letters
ISSN: 1873-3468
Titre abrégé: FEBS Lett
Pays: England
ID NLM: 0155157
Informations de publication
Date de publication:
25 Jun 2024
25 Jun 2024
Historique:
revised:
24
05
2024
received:
01
05
2024
accepted:
05
06
2024
medline:
26
6
2024
pubmed:
26
6
2024
entrez:
26
6
2024
Statut:
aheadofprint
Résumé
Mitochondrial NADH-ubiquinone oxidoreductase (complex I) couples electron transfer from NADH to ubiquinone with proton translocation in its membrane part. Structural studies have identified a long (~ 30 Å), narrow, tunnel-like cavity within the enzyme, through which ubiquinone may access a deep reaction site. Although various inhibitors are considered to block the ubiquinone reduction by occupying the tunnel's interior, this view is still debatable. We synthesized a phosphatidylcholine-quinazoline hybrid compound (PC-Qz1), in which a quinazoline-type toxophore was attached to the sn-2 acyl chain to prevent it from entering the tunnel. However, PC-Qz1 inhibited complex I and suppressed photoaffinity labeling by another quinazoline derivative, [
Identifiants
pubmed: 38924556
doi: 10.1002/1873-3468.14967
doi:
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Subventions
Organisme : Japan Society for the Promotion of Science
ID : 21H02130
Organisme : Japan Society for the Promotion of Science
ID : 22H02273
Organisme : Japan Society for the Promotion of Science
ID : 24K08729
Informations de copyright
© 2024 The Author(s). FEBS Letters published by John Wiley & Sons Ltd on behalf of Federation of European Biochemical Societies.
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