Cooperation of a "reactive Oxygen Cycle" with the Q Cycle and the Proton Cycle in the Respiratory Chain--superoxide Generating and Cycling Mechanisms in Mitochondria

Based on our recent findings concerning the generating, partitioning, targeting, and functioning of superoxide in mitochondria, a hypothetical model involving a "reactive oxygen cycle" in the respiratory chain has been proposed (Liu and Huang, 1991, 1996; Liu et al., 1996; Liu, 1997, 1998) This model emphasizes that during State 4 respiration, an interaction between an electron leak (a branch of electron transfer directly from the respiratory chain to form O2*-, but not H2O) and a proton leak (a branch pathway which utilizes delta muH+ to produce heat, but not ATP) may take place in cooperation with the Q and proton cycles in mitochondria through the consumption of H+ by O2*- anions to form a protonated perhydroxyl radical, HO2, which is directly permeable across the inner mitochondrial membrane and induces proton leakage and a decrease of delta muH+. O2*- generation in the mitochondrial respiratory chain and its cycling across the inner membrane may have the role of an endogenous protonophore in regulating and partitioning energy transduction and heat production, as well as in pathogenesis of mitochondrial diseases, aging, and apoptosis. The present article summarizes the supporting experimental evidence obtained in this laboratory and presents a brief description of the theoretical basis of this model.