Mitochondrial Transplantation: From Energy Replacement to Immune Reprogramming

Mitochondrial transplantation—the direct transfer of healthy mitochondria into damaged cells—is emerging from experimental curiosity to therapeutic possibility. This review in Pharmacological Research surveys how the approach has evolved from simple energy replacement to a more sophisticated strategy involving metabolic and immune system reprogramming. Mitochondrial dysfunction is a hallmark of aging, contributing to neurodegeneration, heart disease, and systemic frailty. Early transplantation studies focused on rescuing ATP production in energy-starved tissues. Recent work reveals transplanted mitochondria also modify inflammatory signaling and metabolic pathways, potentially addressing root causes rather than just symptoms. The technique has shown promise in animal models of stroke, heart attack, and neurodegenerative disease. Some human pilot studies in cardiac surgery patients have reported safety and preliminary efficacy signals. However, major questions persist: How long do transplanted mitochondria survive? Do they integrate into existing networks or function independently? What's the optimal source—autologous vs. allogeneic? For longevity applications, mitochondrial transplantation could theoretically rejuvenate aged tissues if technical hurdles around delivery, dosing, and persistence are solved. It remains experimental but represents creative thinking about directly repairing aging's cellular machinery.