Fig. 7: A cartoon summarising our findings.

During the progression of AP, FAT10 expression is upregulated. It competes with ubiquitin for binding to NCOA4, thereby antagonising its ubiquitination and forming a stable FAT10-NCOA4 complex that is not degraded via the proteasomal pathway. This results in increased NCOA4 expression, which in turn promotes ferroptosis in pancreatic acinar cells. Silibinin, by targeting and inhibiting the FAT10-NCOA4 pathway, can suppress ferroptosis in pancreatic acinar cells.