Mitochondrial transfer: a novel paradigm for wound healing

Abstract Mitochondria not only serve as cellular powerhouses and metabolic regulatory hubs but also play crucial roles in calcium homeostasis, apoptosis regulation, and signal transduction. During wound repair, mitochondria modulate inflammatory and immune responses; drive angiogenesis; and supply energy for the proliferation, differentiation, and migration of repair cells such as fibroblasts and epithelial cells. When mitochondrial dysfunction exceeds the self-regulatory capacity, cellular energy deficits, metabolic disturbances, dysregulated signaling, and oxidative stress damage occur. These abnormalities collectively impair cellular repair mechanisms, ultimately contributing to chronic nonhealing wounds. Historically, mitochondria were thought to be acquired via vertical inheritance through cell division or mitochondrial biogenesis. However, the discovery of intercellular mitochondrial transfer provides novel insights into mitochondrial acquisition and presents new avenues for rescuing mitochondrial dysfunction. This article comprehensively reviews the dialectical relationship between mitochondrial dysfunction and impaired wound healing by integrating mechanisms of mitochondrial transfer, including modes, triggers, and regulatory pathways. It further highlights the therapeutic potential of mitochondrial transfer in wound repair. Additionally, this article provides forward-looking perspectives on clinical applications and future developments in mitochondrial transfer for wound healing, aiming to establish a theoretical foundation for mitochondrial transplantation therapies.