Mitochondria-Associated mRNAs Restore ATP During Oxidative Stress via Cytosolic Translation

Evidence from laboratory and animal studies provides groundwork for understanding mechanisms and potential before human studies continue.

• Level A · Stronger Clinical Evidence
• Level B · Emerging clinical evidence with positive signals
• Level C · Early human research exploring benefits
• Level D · Scientific groundwork from lab and animal studies
• Emerging · Emerging topic under active research

Abstract (original English)

Mitochondrial transplantation has been proposed as a strategy to restore cellular bioenergetics after oxidative injury, but the mechanisms governing ATP recovery remain unclear. Using placental mitochondria, we examined ATP restoration following H 2 O 2 -induced oxidative stress. Unmodified mitochondria modestly increased ATP under baseline conditions but failed to restore ATP after injury. In contrast, lipid-coated mitochondria (MitoCoat) and lipid-encapsulated mitochondria-associated mRNAs (MitoCoat-mRNA) significantly increased ATP levels in injured cells. Transcriptomic analyses revealed that ATP recovery occurred without the normalization of canonical glycolytic or oxidative phosphorylation (OXPHOS) gene programs. Instead, unmodified mitochondria induced broad transcriptional responses associated with immune activation and cellular stress, whereas MitoCoat elicited a more restricted transcriptional profile. Notably, mitochondria-associated mRNAs alone restored ATP without detectable changes in host transcriptional programs. The removal of mitochondrial surface-associated ribosomes or the inhibition of cytosolic but not mitochondrial translation attenuated ATP recovery. The restoration of key metabolic enzymes through cytosolic translation, including PFKP, pyruvate dehydrogenase, and ATP synthase subunit ATP5A suggests that mitochondria-associated mRNAs promote recovery by

Evidence level

Evidence from laboratory and animal studies provides groundwork for understanding mechanisms and potential before human studies continue.

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