TRIM32 promotes neuronal ferroptosis by enhancing K63-linked ubiquitination and subsequent p62-selective autophagic degradation of GPX4.

ABSTRACT: Ferroptosis, characterized by iron-dependent phospholipid peroxidation, is recognized as one of the cell death pathways activated following spinal cord injury (SCI). However, the precise regulatory mechanisms governing this process remain poorly understood. Here, this study identified TRIM32, an E3 ubiquitin ligase, as a key enhancer of neuronal ferroptosis. TRIM32 promoted neuronal ferroptosis by accelerating the degradation of GPX4, which is an essential inhibitor of ferroptosis. Conditional deletion of Trim32 in neurons markedly inhibited neuronal ferroptosis and promoted neuronal survival, eventually improving mouse locomotor functional recovery after SCI. However, overexpression of Trim32 showed aggravated neuronal loss and poor behavioral function, which could be attenu

SUBMITTER: Zhou X 

PROVIDER: S-EPMC11781169 | biostudies-literature | 2025

REPOSITORIES: biostudies-literature