Figure 5
Impairment of the electron transport chain in Alzheimer's disease. Complexes I (NADH:ubiquinone oxidoreductase) and II (succinate dehydrogenase, belongs to the tricarboxylic acid (TCA) cycle) receive electrons from NADH and FADH2, respectively. Electrons are then driven from complexes by the mobile carrier molecules coenzyme Q/ubiquinone (UQ) and cytochrome c (Cyt c) to the final acceptor, molecular oxygen (O2). Electron flow is coupled to proton movement across the inner mitochondrial membrane (IMM) in complexes I, III and IV. The resulting proton gradient is harvested by complex V to generate ATP. In Alzheimer's disease, abnormal mitochondrial electron activities have been observed, predominantly in complexes I and IV, leading to impaired mitochondrial membrane potential, decreased production of ATP (complex V) and enhanced reactive oxygen species (ROS) levels. Interestingly, deregulation of complex I is mainly tau-dependent, while deregulation of complex IV is amyloid-β (Aβ)-dependent, at both the protein and activity level. IMS, intermembrane space.