Fig. 6.

ROS production by the electron transport chain (ETC): role of mitochondrial proton motive force (∆ψ). Electron carriers, NADH and FADH₂ feed electrons (e⁻) into complex I and complex II of the ETC, respectively. As e⁻ traverse through the ETC they release some of their energy to pump H⁺ into the intermembrane space generating a ∆ψ. The ∆ψ is used to move H⁺ through ATP synthase and phosphorylate ADP to ATP. At several points along the ETC (esp. complex I and III) there is a potential for e⁻ to leak and reduce O₂ to superoxide (${\mathrm{O}}_2^{·-}$). The rate of ${\mathrm{O}}_2^{·-}$ production is directly related to the level of ∆ψ; ∆ψ was varied using an uncoupling agent or inhibitors of ETC (inset; from Korshunov et al. [318]). A feedback mechanism exists to limit ${\mathrm{O}}_2^{·-}$ production by dissipating the ∆ψ. In this scenario, excessive ${\mathrm{O}}_2^{·-}$ production activates the uncoupling protein (UCP) allowing H⁺ to diffuse back into the matrix bypassing the ATP synthase. The increased efflux of H⁺ lowers the ∆ψ and reduces ${\mathrm{O}}_2^{·-}$ production. Red arrows, forward e⁻ flow; red dashed arrow, reverse electron flow; Q, Coenzyme Q; Cyt, cytochrome c. (modified from Krauss et al. [326] and Chen and Zweier [298]).