A small fraction of electrons leave the electron transport chain before reaching complex IV. Premature electron leakage to oxygen results in the formation of superoxide. The relevance of this otherwise minor side reaction is that superoxide and other reactive oxygen species are highly toxic and are thought to play a role in several pathologies, as well as aging (the free radical theory of aging). Electron leakage occurs mainly at the Q site and is stimulated by antimycin A. Antimycin A locks the b hemes in the reduced state by preventing their re-oxidation at the Q site, which, in turn, causes the steady-state concentrations of the Q semiquinone to rise, the latter species reacting with oxygen to form superoxide. The effect of high membrane potential is thought to have a similar effect. Superoxide produced at the Qo site can be released both into the mitochondrial matrix and into the intermembrane space, where it can then reach the cytosol. This could be explained by the fact that Complex III might produce superoxide as membrane permeable HOO rather than as membrane impermeable O.