OTUB1 Modulates Ferroptosis by Regulating SLC7A11 Ubiquitination in Pancreatic β-Cells.

ABSTRACT: Ferroptosis, a regulated form of cell death driven by iron-dependent lipid peroxidation, plays a significant role in pancreatic β-cell failure associated with diabetes. In this study, we investigated how 2-deoxy-d-ribose (dRib) induces ferroptosis in β-cells and identified the OTUB1-SLC7A11 axis as a critical regulatory mechanism. Using rat insulinoma-derived RIN5mF cells and isolated rat islets, we found that dRib exposure markedly impaired cystine uptake via system χc^-, resulting in intracellular glutathione (GSH) depletion, accumulation of lipid peroxidation products such as malondialdehyde and 4-hydroxynonenal, and increased lipid reactive oxygen species (ROS). Although SLC7A11 mRNA levels were upregulated, its protein levels were reduced due to increased ubiquitination and

SUBMITTER: Yoo S 

PROVIDER: S-EPMC12516175 | biostudies-literature | 2025 Oct

REPOSITORIES: biostudies-literature