Figure 1.

Illustrates the ROS generation in the mitochondrion. The mitochondrial ETC consists of five multi-subunit enzyme complexes located in the IMM. Electrons donated by NADH and FADH₂ during the TCA cycle are shuttled to ETC components, initiating at complex I (NADH ubiquinone reductase) or complex II (succinate dehydrogenase), and then sequentially passing through complex III (ubiquinol-cytochrome c reductase) and complex IV (cytochrome c oxidase), finally reaching complex V (F0F1 ATP synthase), where they are finally transferred to oxygen. This electron transfer process is closely associated with proton transport across the inner membrane, establishing an electrochemical gradient crucial for ATP generation. Under normal conditions, mitochondria efficiently metabolize oxygen, producing ROS such as O₂^•−, which serves as the primary ROS. O₂^•− is then converted to H₂O₂ by SOD within the mitochondria. Subsequently, H₂O₂ is further metabolized to water by enzymes such as GPx−GR, Prx−Trx−TrxR, or catalase. However, excessive ROS production can lead to oxidative damage to proteins, lipids, and mtDNA.