ArticleCurrent biology : CB2015
Polarized cell motility induces hydrogen peroxide to inhibit cofilin via cysteine oxidation.
Article in Current biology : CB, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 51 papers.
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Who cites it
51 citing papers in PubMed, 82 citations in OpenAlex.
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- Cofilin-1 is a redox-sensitive guard of the NLRP3 inflammasome.Nature immunology · 2026Article
- The Pro-Metastatic Roles of ROS.Antioxidants (Basel, Switzerland) · 2026Review
- FIMBRIN2 Regulates ABA-Induced Stomatal Closure by Promoting Microfilament Bundling and Turnover in Arabidopsis Guard Cells.Plant direct · 2026Article
- Redox regulation of cell migration via Nischarin S-glutathionylation.Free radical biology & medicine · 2026Article
- A mechanism for the disrupted redox regulation of vascular contractility during aging.iScience · 2026Article
- Redox Regulation of Cell Migration via Nischarin S-glutathionylation.bioRxiv : the preprint server for biology · 2025Article
- 12/15-Lipoxygenase-Derived Electrophilic Lipid Modifications in Phagocytic Macrophages.ACS chemical biology · 2025Article
- The role of mitochondria in tumor metastasis and advances in mitochondria-targeted cancer therapy.Cancer metastasis reviews · 2024Review
- Protein phosphatase PP2Cα S-glutathionylation regulates cell migration.The Journal of biological chemistry · 2024Article
- E-Cadherin Induces Serine Synthesis to Support Progression and Metastasis of Breast Cancer.Cancer research · 2024Article
- Emerging roles of deubiquitinating enzymes in actin cytoskeleton and tumor metastasis.Cellular oncology (Dordrecht, Netherlands) · 2024Review
- Therapy-induced senescence through the redox lens.Redox biology · 2024Review
- Protein disulfide isomerase A1 regulates fenestration dynamics in primary mouse liver sinusoidal endothelial cells (LSECs).Redox biology · 2024Article
- Loss of Myo19 increases metastasis by enhancing microenvironmental ROS gradient and chemotaxis.EMBO reports · 2024Article
- N-terminal α-amino SUMOylation of cofilin-1 is critical for its regulation of actin depolymerization.Nature communications · 2023Article
- Loss of cell-cell adhesion triggers cell migration through Rac1-dependent ROS generation.Life science alliance · 2023Article
- Synthesis and Use of the Bifunctional Sulfenic Acid Probe BCN-E-BCN for In Vitro and Cell-Based Assays of Protein Oxidation.Current protocols · 2022Article
- Mitochondrial Fission and Fusion in Tumor Progression to Metastasis.Frontiers in cell and developmental biology · 2022Review
Corrections and comments
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Authors and funding
10 authors at 4 institutions in 1 country.
Funding
Abstract
Mesenchymal cell motility is driven by polarized actin polymerization [1]. Signals at the leading edge recruit actin polymerization machinery to promote membrane protrusion, while matrix adhesion generates tractive force to propel forward movement. To work effectively, cell motility is regulated by a complex network of signaling events that affect protein activity and localization. H2O2 has an important role as a diffusible second messenger [2], and mediates its effects through oxidation of cysteine thiols. One cell activity influenced by H2O2 is motility [3]. However, a lack of sensitive and H2O2-specific probes for measurements in live cells has not allowed for direct observation of H2O2 accumulation in migrating cells or protrusions. In addition, the identities of proteins oxidized by H2O2 that contribute to actin dynamics and cell motility have not been characterized. We now show, as determined by fluorescence lifetime imaging microscopy, that motile cells generate H2O2 at membranes and cell protrusions and that H2O2 inhibits cofilin activity through oxidation of cysteines 139 (C139) and 147 (C147). Molecular modeling suggests that C139 oxidation would sterically hinder actin association, while the increased negative charge of oxidized C147 would lead to electrostatic repulsion of the opposite negatively charged surface. Expression of oxidation-resistant cofilin impairs cell spreading, adhesion, and directional migration. These findings indicate that H2O2 production contributes to polarized cell motility through localized cofilin inhibition and that there are additional proteins oxidized during cell migration that might have similar roles.
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