Kinetic characterization of mitochondrial complex I inhibitors using annonaceous acetogenins

Citation
Jr. Tormo et al., Kinetic characterization of mitochondrial complex I inhibitors using annonaceous acetogenins, ARCH BIOCH, 369(1), 1999, pp. 119-126
Citations number
33
Categorie Soggetti
Biochemistry & Biophysics
Journal title
ARCHIVES OF BIOCHEMISTRY AND BIOPHYSICS
ISSN journal
00039861 → ACNP
Volume
369
Issue
1
Year of publication
1999
Pages
119 - 126
Database
ISI
SICI code
0003-9861(19990901)369:1<119:KCOMCI>2.0.ZU;2-4
Abstract
The NADH:ubiquinone oxidoreductase (complex I) of the mitochondrial respira tory chain is by far the largest and most complicated of the proton-translo cating enzymes involved in the oxidative phosphorylation. Many clues regard ing the electron pathways from matrix NADH to membrane ubiquinone and the l inks of this process with the translocation of protons are highly controver sial. Different types of inhibitors become valuable tools to dissect the el ectron and proton pathways of this complex enzyme. Therefore, further knowl edge of the mode of action of complex I inhibitors is needed to understand the underlying mechanism of energy conservation. This study presents for th e first time a detailed exploration of the inhibitory action of the Annonac eous acetogenins, the most powerful inhibitors of the mammalian enzyme, tak ing as the head-series rolliniastatin-1, rolliniastatin-2, and corossolin. Despite their close chemical resemblance, each of them inhibits the complex I with different kinetic features reflecting differential binding to the e nzyme. (C) 1999 Academic Press.