Mitochondrial Dysfunction and β-Cell Failure in Type 2 Diabetes Mellitus

Figure 1

Mitochondrial ROS production and defense. The electron transport chain consists of four protein complexes (I–IV) and the ATP synthase located in the inner mitochondrial membrane (IMM). The activity of complex I converts NADH to NAD⁺, and the activity of complex II converts succinate to fumarate. Complexes I, III, and IV transport protons (H⁺) across the membrane, and complexes I and III generate superoxide anion radical (O₂^•−) during the electron transfer process. O₂^•− can naturally dismutate to hydrogen peroxide (H₂O₂) or is enzymatically dismutated by matrix manganese superoxide dismutase (MnSOD). O₂^•− is not membrane permeable but can pass through inner membrane ion channel (IMAC) and is dismutated to H₂O₂ by Cu/ZnSOD in the intermembrane space (IMS)/cytoplasm. H₂O₂ is detoxified in the matrix by catalase and the glutathione peroxidase (GPx). Alternately, H₂O₂ can react with metal ions to generate via Fenton chemistry (dash line) the highly reactive hydroxyl radical (•OH) that can initiate the peroxidation of the inner mitochondrial membrane phospholipids, such as cardiolipin. Cyt. c: cytochrome c; IMS: intermembrane space; GSH: glutathione; GSSG: glutathione disulfide; ΔΨ_𝑚: membrane potential.