Modulation of the mitochondrial cytochrome bc1 complex activity by chromanols and related compounds.
Chem Res Toxicol
; 23(1): 193-202, 2010 Jan.
Article
en En
| MEDLINE
| ID: mdl-20014750
ABSTRACT
Tocopherols (alpha-, beta-, gamma-, and delta-Toc) and tocopheryl quinones (alpha-, beta-, gamma-, and delta-TQ) were recently suggested to modulate mitochondrial electron transfer in mammals. Intriguingly, Tocs and stigmatellin, a potent inhibitor of the mitochondrial cytochrome (cyt) bc(1) complex, possess a common structural feature the chroman core. Therefore, we studied the interference of Tocs as well as synthetic model compounds (low molecular weight TQ analogues and tetramethyl chromanones) at the mitochondrial cyt bc(1) complex. Enzymatic experiments revealed that besides the inhibitor stigmatellin, among natural vitamin E-related derivatives, gamma-TQ/delta-TQ and, among synthetic compounds, TMC2O (6-hydroxy-4,4,7,8-tetramethyl-chroman-2-one) were most effective in decreasing the cyt bc(1) activities. Stopped-flow photometric and low-temperature electron paramagnetic resonance spectroscopic experiments showed for TMC2O an inhibition of electron transfer to cyt c(1) and a modulation of the environment of the Rieske iron-sulfur protein (ISP). Docking experiments suggest a binding interaction of the 6-OH group and 1-O atom/2-C( horizontal lineO) group of TMC2O with Glu-271 (cyt b) and His-161 (ISP) in the cyt bc(1) complex, respectively. This binding pose is similar but not identical to the potent inhibitor stigmatellin. The data suggest that chroman-2-ones are possible templates for modulatory molecules for the cyt bc(1) target.
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Complejo III de Transporte de Electrones
/
Tocoferoles
/
Antioxidantes
Límite:
Animals
Idioma:
En
Revista:
Chem Res Toxicol
Asunto de la revista:
TOXICOLOGIA
Año:
2010
Tipo del documento:
Article
País de afiliación:
Austria