Cherimolin-1, new selective inhibitor of the first energy-coupling site of the NADH: ubiquinone oxidoreductase (complex I).
The mechanism linking electron transport to proton translocation in the NADH:ubiquinone oxidoreductase (complex I of the mitochondrial respiratory chain) is still unclear. Inhibitors acting at different sites of the enzyme are powerful tools to clarify this mechanism. Up to now, a unique inhibitor, the Annonaceous acetogenin rolliniastatin-2, selectively blocks the most internal proton-translocation site. This study introduces cherimolin-1, a new acetogenin that inhibits the complex I with this special mode of action, which is more easily available from the plant material. Moreover, the mode of action of this scarce type of complex I inhibitor is further characterized.
Estornell
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Departament de Bioquímica i Biologia Molecular, Facultat de Farmàcia, Universitat de València, Burjassot, Spain. Ernesto.Estornell@uv.es
Tormo
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JR
Cortes
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D000818:Animals; D001665:Binding Sites / Q000187:drug effects; D002417:Cattle; D004734:Energy Metabolism / Q000187:drug effects; D005638:Fruit / Q000737:chemistry*; D005663:Furans / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*; D007783:Lactones / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*; D016660:NAD(P)H Dehydrogenase (Quinone) / Q000037:antagonists & inhibitors* / Q000378:metabolism; D010936:Plant Extracts / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*; D013329:Structure-Activity Relationship
D005663:Furans; D007783:Lactones; D010936:Plant Extracts; C109215:cherimolin-1; C061022:bullatacin; D016660:NAD(P)H Dehydrogenase (Quinone)