PGC-1α protects against MASH via Tim23-dependent inhibition of DRP1-mediated ferroptosis - PubMed
4 hours ago
- #MASH
- #mitochondrial function
- #ferroptosis
- PGC-1α plays a crucial role in protecting against MASH by inhibiting DRP1-mediated ferroptosis through Tim23-dependent mechanisms.
- Hepatocyte ferroptosis is observed in MASH patients and models, characterized by down-regulated Tim23 and up-regulated ACSL4 expression.
- PGC-1α deficiency worsens hepatocyte ferroptosis in MASH models, while its overexpression mitigates the condition.
- Mechanistically, PGC-1α promotes Nrf1 binding to the Tim23 promoter, reducing Drp1 transcription and ACSL4 mitochondrial translocation, thereby inhibiting ferroptosis.
- The study highlights PGC-1α's potential as a therapeutic target for MASH by modulating mitochondrial function and ferroptosis pathways.