Figure 2.

OS triggers mitochondrial dysfunction and leads to MN degeneration. The invasion of abnormal substances such as H2S, SOD, Catalase (CAT), and ROS causes cells to generate OS, resulting in the enhancement of PINK1-Parkin-mediated mitophagy and the accumulation of mitochondrial damage. Simultaneously, mitochondrial damage in turn causes thiol oxidation, triggering the cascading effects of Ca²⁺ imbalance and mitochondrial membrane rupture, which activates cell death. In addition, the impairment of ETC due to mitochondrial damage reduces the production of NAD⁺ and ATP, and increases the production of ROS, resulting in abnormal protein aggregation, mtDNA mutation, and structural deformity, and eventually leads to motor neuron degeneration.