Intercellular mitochondrial transfer rewires redox signaling and metabolic plasticity: mechanisms, disease relevance and therapeutic frontiers

Evidence from laboratory and animal studies provides groundwork for understanding mechanisms and potential before human studies continue.

• Level A · Stronger Clinical Evidence
• Level B · Emerging clinical evidence with positive signals
• Level C · Early human research exploring benefits
• Level D · Scientific groundwork from lab and animal studies
• Emerging · Emerging topic under active research

Abstract (original English)

Intercellular mitochondrial transfer is recognized as a central mechanism that shapes redox homeostasis, metabolic plasticity, and cellular resilience across multiple tissues. Through tunneling nanotubes (TNTs), extracellular vesicles (EVs), gap junction channels (GJCs), and cell fusion, mitochondria move between donor and recipient cells to restore bioenergetic capacity, buffer oxidative stress, and tune redox-sensitive signaling networks. Recent work has begun to clarify the regulatory framework governing donor-recipient specificity, cargo selection, and the stress-activated cues that trigger organelle exchange. Mitochondrial transfer also exerts distinct, context-dependent influences on disease trajectories. It mitigates injury in neurological damage, ischemia-reperfusion conditions, immune dysfunction, aging, and inflammatory pain, largely by reprogramming mitochondrial function and reactive oxygen species (ROS) dynamics. Conversely, in cancer, mitochondrial acquisition enhances metabolic flexibility, invasiveness, and resistance to therapy. Current therapeutic approaches, including mitochondrial transplantation, EV-based delivery systems, and mitochondria-enhanced immune cells, highlight the translational potential of manipulating mitochondrial exchange, yet face challenges such as mitochondrial fragility, inefficient targeting, and immunogenicity. Deeper mechanistic insig

Evidence level

Evidence from laboratory and animal studies provides groundwork for understanding mechanisms and potential before human studies continue.

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