Intracellular mitochondrial transfer in ischemic stroke: Mechanisms and therapeutic application

BACKGROUND: Current therapeutic models for ischemic stroke (IS) are shifting from a narrow focus on neuroprotection to a broader concept of cytoprotection. This new paradigm emphasizes rescuing damaged brain cells and maintaining their structural and functional integrity through organelle transfer between healthy and damaged cells. Mounting evidence have supported that intracellular mitochondrial transfer is an intrinsic response to IS, playing a critical role in mitigating neural damage. Consequently, mitochondrial transplantation from stem cell is emerging as a therapeutic avenue for IS. AIM OF REVIEW: This article reviews the IS-induced mitochondrial dysfunction, the modes and mechanisms of endogenous intracellular mitochondrial transfer, and recent advances in using stem cell-derived mitochondrial transplantation to treat IS. KEY SCIENTIFIC CONCEPTS: This review emphasizes the dual roles of mitochondrial transfer in determining neural cells fate and neurological function recovery following IS. On one hand, health cells can donate intact mitochondria to damaged cells, to revitalize them by restoring cell metabolic function. On the other hand, damaged cell may expel dysfunction mitochondria, which can be cleared by healthy neighbors or, alternatively propagate injury. We discuss the current challenges in this field and propose that enhancing healthy mitochondrial transfer or preventing damaged mitochondrial release may hold great potential for alleviating IS injury.