Mitochondria-associated mRNAs restore ATP during oxidative stress via cytosolic translation
Mitochondrial transplantation has been explored as a potential way to help cells recover energy after oxidative damage, but how it restores ATP remains unclear. In this study, we used mitochondria derived from placenta to examine ATP recovery following oxidative stress. We found that unmodified mitochondria had only a limited effect and did not restore ATP after injury. In contrast, mitochondria that were coated with lipids, as well as lipid-encapsulated mitochondrial mRNAs, significantly improved ATP levels in damaged cells. Further analysis showed that this recovery did not depend on reactivating typical energy-producing gene programs. Instead, unmodified mitochondria triggered broad stress and immune responses, while the coated versions caused much more limited changes. Notably, mitochondrial mRNAs alone were able to restore ATP without altering overall gene expression in the cell. Additional experiments indicated that this effect relies on protein production in the cell cytoplasm, helping to rebuild key metabolic enzymes and restore coordination between energy pathways. Overall, these findings suggest that delivering mitochondrial-associated mRNAs may be a promising strategy to restore cellular energy under conditions of oxidative stress.