Molecular mechanisms of ALDH3A1-mediated cellular protection against 4-hydroxy-2-nonenal

► Expression of ALDH3A1 in corneal stromal fibroblasts protects cells from 4-hydroxy-2-nonenal (4-HNE)-induced cytotoxicity. ► 4-HNE is effectively metabolized by ALDH3A1. ► ALDH3A1 prevents 4-HNE protein adduction. ► ALDH3A1 limits 4-HNE-induced glutathione depletion and inhibitory effects on proteasome activity.