Mitochondrial dysfunction in immune cells during the perioperative period: mechanisms, emerging therapeutic strategies, and implications for multi-organ protection.

Mitochondrial health is increasingly recognized as a critical determinant of immune competence during the perioperative period. Surgical interventions impose unique metabolic and inflammatory stresses-such as ischemia-reperfusion injury, anesthetic exposure, and systemic inflammatory responses-that impair immune cell bioenergetics and redox balance. Dysfunctional mitochondria in neutrophils, macrophages, and T lymphocytes alter cytokine production, phagocytic activity, and antigen presentation, tipping the balance toward excessive inflammation or postoperative immunosuppression, thereby exacerbating organ injury. This review integrates current knowledge of the mechanisms linking perioperative mitochondrial dysfunction to immune dysregulation, and systematically evaluates emerging therapeutic strategies, including mitochondrial-targeted antioxidants, permeability transition pore inhibitors, metabolic reprogramming agents, mitochondrial transplantation, and gene-based interventions. By bridging experimental evidence with translational and early clinical studies in cardiac, neurological, hepatic, and renal surgeries, we argue that precise modulation of immune cell mitochondrial function represents a promising and underexplored frontier for comprehensive perioperative organ protection.