Effect of electron transfer inhibitors on superoxide generation in the cytochrome bc₁ site of the mitochondrial respiratory chain

Abstract

Antimycin, 2‐nonyl‐4‐hydroxyquinoline N‐oxide and funiculosin induce O·− 2 generation by submitochondrial particles oxidizing succinate, whereas KCN, mucidin, myxothiazol or 2,3‐dimercaptopropanol inhibit O·− 2 generation. Thenoyltrifluoroacetone does not induce superoxide production by itself but slightly stimulates the reaction initiated by antimycin. The results indicate that auto‐oxidation of unstable ubisemiquinone formed in centre o of the Q‐cycle generates most of the O·− 2 radicals in the cytochrome bc 1‐site of the mitochondrial respiratory chain.

The Mitochondrial Production of Reactive Oxygen Species: Mechanisms and Implications in Human Pathology

“…2). In agreement with this interpretation, studies in CoQ-depleted and reconstituted mitochondria in- 10 , produce the same amount of superoxide as CoQ-depleted mitochondria, indicating that endogenous CoQ 10 is not a source of ROS.…”

“…In the Q-cycle scheme of electron transfer in the bc1 complex (9), antimycin A blocks ubiquinone reduction by cytochrome b 562 at center i , at the inner or negative side of the membrane. The antimycin-stimulated production of ROS is inhibited by inhibitors acting at center o (outer or positive side), such as myxothiazol and stigmatellin, where ubiquinol reduces both the Rieske iron-sulfur cluster and cytochrome b 566 (10). According to the Q-cycle, the site of one-electron reduction of oxygen in presence of antimycin is located at a component at center o, thus explaining the inhibition of antimycin-stimulated ROS production by center o inhibitors (Fig.…”

Inhibition of mitochondrial respiratory chain complex I by TNF results in cytochrome c release, membrane permeability transition, and apoptosis

“…An increase in electron¯ow upregulates the generation of ROS from MRC (Ksenzenko et al, 1983;Turrens and Boveris, 1980). To investigate whether oxidative stress is involved at a step subsequent to complex I inhibition, the e ect of antioxidant PDTC on TNFand rotenone-induced apoptosis was tested.…”

Cardiac H11 kinase/Hsp22 stimulates oxidative phosphorylation and modulates mitochondrial reactive oxygen species production: Involvement of a nitric oxide-dependent mechanism

“…This hypothesis was reinforced by the investigation of the capacity of complex III from TG mice to produce superoxide. This was performed by measuring superoxide production in the presence of antimycin A, an inhibitor of complex III which induces a high superoxide production from the Q 0 center of complex III [21].…”