The relationship between amyloid-β (Aβ), mitochondrial electron transport chain (ETC), and superoxide (O2 −∙) formation. As electrons are transferred through complexes I, III, and IV, protons are pumped into the inner membrane space, generating an electrochemical gradient. The energy stored is used to generate ATP via complex V (ATP synthase). Damage to components of the ETC can lead to a stalling of reduced intermediates which increases the probability of electrons slipping and reducing O2 to form superoxide. Aβ has been shown to directly inhibit complex IV which would lead to bioenergetic impairment and increased formation of reactive oxygen species.
