Emerging Design Principles at the Forefront of Mitochondrial Transplantation Using Engineering Methodologies: Current Achievements and Future Directions

Mitochondrial transplantation has gathered much attention as therapeutics to improve multiple mitochondrial functions simultaneously. While the administration of naked mitochondria into the target tissue has demonstrated therapeutic outcomes sufficient to advance to clinical trials, there remain many limitations, including a low cellular uptake efficiency in the target tissue and dysfunction of the isolated mitochondria. To address these issues, engineering approaches have been developed to functionalize the isolated mitochondria. In this review, we focus on the three critical topics for efficient mitochondrial transplantation and outline emerging design rules and their limitations for each purpose: (i) tissue targeting, (ii) protection of mitochondria from external stresses, and (iii) improvement of cellular uptake efficiency. From these achievements, we also discuss the current limitations of mitochondrial transplantation and propose the future direction of the attractive therapeutic methodology.