Fig. 1.

Diagram of electron leakage in brain disease. Electrons in the mitochondrial ETC are transferred along a series of four protein complexes (Complexes I-IV) with the aid of electron transporters NADH, FADH2, ubiquinone (Co-enzyme Q10, CoQ), and cytochrome c (Cyt c). As a result of this electron transfer, protons are pumped by Complexes I, III, and IV from the mitochondrial matrix into the intermembrane space, thereby generating an electrochemical gradient across the inner mitochondrial membrane. This gradient is used to propel ATP synthase (Complex V) to produce ATP. Although this process is highly efficient, electrons can escape from Complex I and Complex III and be transferred to O₂, which is reduced to the radical O2•−. This ROS production is exacerbated under pathological conditions such as brain disease and activates inflammatory processes, thereby establishing a cycle of ROS production, inflammation, and neuronal damage