Mitochondrial respiratory complex I can be inhibited via bypassing the ubiquinone-accessing tunnel.
FEBS Lett
; 598(16): 1989-1995, 2024 Aug.
Article
en En
| MEDLINE
| ID: mdl-38924556
ABSTRACT
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, [125I]AzQ. This study provides further experimental evidence that is difficult to reconcile with the canonical ubiquinone-accessing tunnel model.
Palabras clave
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Ubiquinona
/
Complejo I de Transporte de Electrón
Límite:
Animals
Idioma:
En
Revista:
FEBS Lett
Año:
2024
Tipo del documento:
Article
País de afiliación:
Japón
Pais de publicación:
Reino Unido