Mitochondrial transfer in sepsis: Dual role, mechanistic networks, and translational strategies

Sepsis is a life-threatening clinical syndrome characterized by dysregulated host response, metabolic disturbance, and multiple organ dysfunction. Mitochondrial damage and bioenergetic failure are core pathological events driving sepsis progression. As a critical intercellular communication mechanism, mitochondrial transfer (MT) participates in mitochondrial quality control, energy homeostasis, and inflammatory regulation under septic stress. This review systematically summarizes the structural and functional mitochondrial injury in sepsis and endogenous quality control pathways. We focus on the four major MT routes, their crosstalk, and regulatory networks. The dual role of MT in sepsis is highlighted: functional MT supports tissue repair and organ protection, while damaged MT amplifies inflammation and exacerbates organ injury. We further outline current strategies to optimize MT-based therapy, including donor cell preconditioning, carrier engineering, and direct mitochondrial modification, as well as biosafety and translational challenges. This review provides an integrated theoretical framework and practical strategies for mitochondria-targeted interventions in sepsis.