Mitochondrial Quality Control in Traumatic Brain Injury: From Mechanisms to Therapeutic Opportunities

Abstract

Traumatic brain injury (TBI) remains a leading cause of death and disability, and secondary injury—evolving over hours to weeks after the insult—constitutes the principal therapeutic window. Mitochondrial dysfunction sits at the hub of this cascade. Mitochondria are actively maintained by an integrated mitochondrial quality control (MQC) system comprising mitochondrial dynamics, mitophagy, and mitochondrial biogenesis, and TBI disrupts every arm of this system. This review summarizes how mitochondrial dysfunction develops after TBI; dissects the three pillars of MQC with emphasis on recent advances such as PINK1/Parkin signalling and receptor-mediated mitophagy; discusses the crosstalk between defective MQC and apoptosis, ferroptosis, pyroptosis, and PANoptosis; and evaluates therapeutic strategies targeting MQC. We further highlight unresolved questions, including the dual, dose-dependent nature of mitophagy, cell-type-specific MQC responses, and the challenge of therapeutic timing. A refined understanding of MQC may help convert mitochondrial biology into clinically useful interventions for TBI.