METTL3-mediated N6-methyladenosine modification of Dnajb1 modulates cardiomyocyte ferroptosis during myocardial infarction - PubMed
4 hours ago
- #epitranscriptomics
- #myocardial infarction
- #ferroptosis
- METTL3-mediated m6A modification of Dnajb1 plays a key role in cardiomyocyte ferroptosis during myocardial infarction (MI).
- DNAJB1 overexpression protects against hypoxia-induced ferroptosis by inhibiting pro-ferroptotic effectors and maintaining glutathione peroxidase 4 (GPX4) stability.
- METTL3 binds to Dnajb1, increasing its m6A modification and reducing mRNA stability, while IGF2BP3 competes to enhance mRNA stability.
- DNAJB1 prevents glutathione depletion and lipid peroxidation by inhibiting GPX4 degradation via the autophagic-lysosomal pathway.
- In vivo, DNAJB1 overexpression improves heart function, reduces infarct size, and lowers oxidative stress markers in MI mice, effects counteracted by METTL3 co-overexpression.
- The study identifies the METTL3/Dnajb1 pathway as a critical regulator of ferroptosis in MI, suggesting potential therapeutic targets.