Vesicle-guided mitochondria: A new perspective for brain mitochondrial transplantation

Mitochondrial activity is essential for the proper functioning of higher brain processes, and its impairment has been linked to a wide range of neurological disorders. Increasing evidence shows that under physiological and pathological conditions, mitochondria can be secreted into the extracellular environment to regulate various biological responses, including cellular bioenergetics. Today, the therapeutic modality known as "mitochondrial transplantation" has emerged as a cutting-edge and highly promising intervention for the promotion of cell and tissue regeneration. This innovative approach entails the replacement of dysfunctional mitochondria in the recipient organism with healthy, functional exogenous mitochondria, thereby aiming to restore cellular function and promote tissue repair and recovery. Several studies have demonstrated the beneficial effects of local or systemic administration of mitochondria on in vitro and in vivo models of brain diseases. We discuss the effect of mitochondrial transplantation in various brain diseases and highlight some critical issues. In this regard, we propose vesicles as a delivery system for both whole mitochondria and mitochondrial components to target cells in the central nervous system. Furthermore, the aim of this review is twofold: firstly, to emphasize the significance of brain mitochondrial transplantation, and secondly, to prompt the scientific community to consider the practical applications of brain mitochondrial transplantation. To this end, the text highlights the as yet unresolved issues and challenges that must be addressed and surmounted if this field is to progress. In conclusion, the authors express their support for the development of new potential therapies for mitochondrial diseases of the central nervous system.