Mitochondrial transplantation: Triumphs, challenges, and impacts on nuclear genome remodelling

作者：Elly H. Shin, Quinn Le, Rachel Barboza, Amanda Morin, Shiva M. Singh, Christina A. Castellani · 发表于：Mitochondrion · 年份：2025 · DOI：10.1016/j.mito.2025.102042 · 被引用次数：7 · 研究领域：Mitochondrial Function and Pathology、Metabolism and Genetic Disorders、Organ Transplantation Techniques and Outcomes

Mitochondria are membrane-bound organelles of eukaryotic cells that play crucial roles in cell functioning and homeostasis, including ATP generation for cellular energy. Mitochondrial function is associated with several complex diseases and disorders, including cardiovascular, cardiometabolic, neurodegenerative diseases and some cancers. The risk for these diseases and disorders is often associated with mitochondrial dysfunction, particularly the quantitative and qualitative features of the mitochondrial genome. Emerging results implicate mito-nuclear crosstalk as the mechanism by which mtDNA variation affects complex disease outcomes. Experimental approaches are emerging for the targeting of mitochondria as a potential therapeutic for several of these diseases, particularly in the form of mitochondrial transplantation. Current approaches to mitochondrial transplantation generally involve isolating healthy mitochondria from donor cells and introducing them to diseased recipients towards amelioration of mitochondrial dysfunction. Using such a protocol, several reports have shown recovery of mitochondrial function and improved disease outcomes post-mitochondrial transplantation, highlighting its potential as a therapeutic method for several complex, severe and debilitating diseases. Additionally, the mitochondrial genome can be modified prior to transplantation to target disease-associated site-specific mutations and to reduce the ratio of mutant-to-WT alleles. These promising ...