Block of electron transport by surangin B in bovine heart mitochondria

Autor: Yanshen Deng, Russell A. Nicholson
Rok vydání: 2005
Předmět:
Zdroj: Pesticide Biochemistry and Physiology. 81:39-50
ISSN: 0048-3575
DOI: 10.1016/j.pestbp.2004.09.001
Popis: Exposure of mitochondria isolated from bovine heart to the insecticidal coumarin surangin B results in inhibition of complex II (IC 50 = 0.2 μM), III (IC 50 = 14.8 μM), and IV (IC 50 = 3.1 μM), but in contrast, the NADH:ubiquinone reductase (complex I) was completely insensitive to this compound at 100 μM. Kinetic analysis of surangin B’s interaction with complex II was then investigated using sub-mitochondrial particles. With succinate as the substrate, surangin B, like carboxin, acted with non-competitive kinetics and clearly contrasted in its action with malonate, a competitive inhibitor of complex II. Likewise, surangin B acted as a non-competitive inhibitor of decylubiquinone-dependent interception of electrons at complex II. Difference spectra of reduced complex III equilibrated with surangin B were found to closely parallel those of antimycin A, but were different in nature to those of the Q o site inhibitors myxothiazol and famoxadone. Investigation of surangin B-dependent functional perturbation of complex III used the synthetic electron acceptor 2-nitrosofluorene, which intercepts electrons specifically from the Q i site. These experiments demonstrated that like antimycin A, surangin B acts as a selective blocker of electron diversion to 2-nitrosofluorene through Q i within complex III. We conclude that surangin B blocks electron transport at several points in bovine heart mitochondria, however, complex I is spared. The potent inhibitory action of surangin B on complex II involves binding to a site which is distinct from both the succinate binding site and the domain responsible for interacting with ubiquinone. Surangin B apparently blocks complex III by interacting with the Q i (antimycin A-binding) pocket.
Databáze: OpenAIRE
Externí odkaz: