Study wrapper · #719
MOTS-c attenuates hyperoxia-induced neonatal cardiac injury by inhibiting oxeiptosis via maintaining the KEAP1-PGAM5 interaction.
Editor's note
In neonatal mice and a rat cardiomyocyte line exposed to high oxygen (hyperoxia), researchers found that MOTS-c lessened oxidative cardiac injury, and that serum MOTS-c fell with hyperoxia. They attribute the protection to inhibition of oxeiptosis, a reactive-oxygen-driven form of cell death, via preservation of the KEAP1-PGAM5 interaction; forcing KEAP1 expression abolished the benefit, supporting KEAP1 as the target. This is a mechanistic, single-model preclinical study. These are preclinical findings; human data are needed before any clinical conclusions can be drawn, and the term "therapeutic agent" in the abstract reflects the authors' framing, not demonstrated clinical benefit. It is consistent with MOTS-c's recurring antioxidant, mitochondria-protective role in animal tissue-injury models.
Plain-language abstract
Newborns given high-oxygen support can suffer oxidative stress that harms the heart. Researchers tested MOTS-c, a mitochondria-made peptide known for antioxidant effects, in newborn mice and in rat heart cells exposed to high oxygen. High oxygen caused heart enlargement, scarring, and dysfunction, alongside a drop in the animals' own MOTS-c levels. Giving MOTS-c reduced this damage and helped restore heart function. The team identified the mechanism as blocking "oxeiptosis," a specific oxygen-stress form of cell death, by keeping two proteins (KEAP1 and PGAM5) bound together and stopping a death-signalling protein from moving into the cell nucleus. When they forced extra KEAP1 into cells, MOTS-c stopped working, pointing to KEAP1 as its key target. All of this was in animals and cells, so it cannot show how MOTS-c would affect human infants; human research would be required. It reinforces MOTS-c's pattern of protecting tissue from oxidative injury.