# Mitochondrial Transplantation as a Therapeutic Strategy for Inherited Mitochondrial Diseases

## TL;DR

This review explores mitochondrial transplantation as a potential treatment for inherited mitochondrial diseases, highlighting its promise and challenges.

## Contribution

The paper systematically evaluates the feasibility and translational requirements of mitochondrial transplantation for mtDNA- and nDNA-based disorders.

## Key findings

- MTx shows beneficial effects in preclinical and early clinical studies for mitochondria-mediated diseases.
- Challenges include the need for repeated administration and addressing technical and ethical issues.
- The review identifies unique translational requirements for chronic inherited mitochondrial disorders.

## Abstract

Mitochondria are essential organelles responsible for cellular energy production and diverse metabolic processes. Mitochondrial dysfunction is implicated in a wide range of diseases. Specifically, genetic mitochondrial diseases, arising from mutations in mitochondrial or nuclear DNA, lead to significant mitochondrial deficits, which result in debilitating and often life‐threatening symptoms. Conventional treatments frequently fail to address these underlying mitochondrial defects, leaving few therapeutic options. Mitochondrial transplantation (MTx), an emerging therapeutic approach involving the delivery of healthy exogenous mitochondria to target cells, has demonstrated beneficial effects in various mitochondria‐mediated diseases in both preclinical and early clinical studies. However, its application to inherited mitochondrial disorders remains largely unexplored and raises important questions about the need for repeated or continuous administration to sustain therapeutic effects. This review systematically examines the potential of MTx for inherited mitochondrial disorders by classifying these diseases by mitochondrial and nuclear DNA origin, critically assessing MTx evidence and mechanisms, and identifying unique translational requirements for chronic inherited disorders. While significant challenges remain, MTx represents a promising approach to directly address mitochondrial dysfunction in these life‐threatening conditions with limited therapeutic alternatives.

Mitochondrial transplantation (MTx) offers a promising therapeutic avenue for mitochondrial diseases. This review comprehensively evaluates MTx, differentiating its feasibility for mtDNA‐ and nDNA‐based disorders. It examines its potential for genetic correction, alongside inherent limitations, technical challenges, and crucial ethical considerations. The review also explores the current landscape and future directions of this innovative strategy.