Mechanism and therapeutic potential of mitophagy in spinal cord injury

Mitochondrial dysfunction is a critical factor in secondary injury following spinal cord injury (SCI). Mitophagy is an essential mechanism for mitochondrial quality control. Proper and timely activation of mitophagy clears damaged mitochondria, reduces oxidative stress and cell death, and provides neuroprotection. However, excessive activation can cause energy depletion and worsen injury. The effects of mitophagy depend on the specificity of its spatial and temporal activation as well as the cellular microenvironment. This review summarizes novel therapeutic strategies targeting mitophagy, including pharmacological modulators, gene-based interventions, biomaterials, and cell therapies. These approaches precisely regulate mitophagy via distinct molecular pathways. Challenges remain in precise regulation, clarification of cell-specific mechanisms, and real-time monitoring in vivo. Future research should aim to develop precise spatiotemporal regulatory tools, identify relevant biomarkers, and integrate mitophagy-targeted therapies with existing methods, providing new insights into SCI treatment.