Vimentin remodeling in response to oxidants and electrophiles is modulated by pH
- Alma E. Martínez
- Paula Martínez-Cenalmor
- Patricia González-Jiménez
- Cristina Vidal-Verdú
- María A. Pajares
- Dolores Pérez-Sala
2026-08-05
Vimentin is critical for cell mechanosensing, cytoskeletal cross-talk, and stress responses and is finely tuned by posttranslational modifications. Vimentin single cysteine, C328, is a modification hotspot, essential for filament remodeling by oxidants and electrophiles. With a p K a near physiological pH, C328 reactivity could depend on cellular pH fluctuations. Here, we show that C328 modifications and vimentin reorganization by thiol-reactive agents are modulated by pH variations in vitro and in cells. Intracellular acidification prevents, whereas alkalinization aggravates, vimentin network disruption by oxidative and electrophilic species, which requires C328. Chemogenetic and optogenetic pH modulation allow spatiotemporal control of vimentin remodeling by oxidants. Moreover, vimentin disassembly at cell edges of migrating fibroblasts and lamellipodia formation are attenuated upon intracellular acidification or expression of a vimentin C328H mutant, which blunts cell migration. Thus, C328 behaves as a coincidental pH- and redox-responsive element, finely tuning vimentin assembly, and supporting the pH dependence of cysteine-mediated redox signaling.