Oxidative stress elicits the remodeling of vimentin filaments into biomolecular condensates.

Autor:	Martínez-Cenalmor P; Department of Cellular and Molecular Biosciences, Centro de Investigaciones Biológicas Margarita Salas, CSIC, 28040, Madrid, Spain., Martínez AE; Department of Cellular and Molecular Biosciences, Centro de Investigaciones Biológicas Margarita Salas, CSIC, 28040, Madrid, Spain., Moneo-Corcuera D; Department of Cellular and Molecular Biosciences, Centro de Investigaciones Biológicas Margarita Salas, CSIC, 28040, Madrid, Spain., González-Jiménez P; Department of Cellular and Molecular Biosciences, Centro de Investigaciones Biológicas Margarita Salas, CSIC, 28040, Madrid, Spain., Pérez-Sala D; Department of Cellular and Molecular Biosciences, Centro de Investigaciones Biológicas Margarita Salas, CSIC, 28040, Madrid, Spain. Electronic address: dperezsala@cib.csic.es.
Jazyk:	angličtina
Zdroj:	Redox biology [Redox Biol] 2024 Sep; Vol. 75, pp. 103282. Date of Electronic Publication: 2024 Jul 23.
DOI:	10.1016/j.redox.2024.103282
Abstrakt:	The intermediate filament protein vimentin performs an essential role in cytoskeletal interplay and dynamics, mechanosensing and cellular stress responses. In pathology, vimentin is a key player in tumorigenesis, fibrosis and infection. Vimentin filaments undergo distinct and versatile reorganizations, and behave as redox sensors. The vimentin monomer possesses a central α-helical rod domain flanked by N- and C-terminal low complexity domains. Interactions between this type of domains play an important function in the formation of phase-separated biomolecular condensates, which in turn are critical for the organization of cellular components. Here we show that several oxidants, including hydrogen peroxide and diamide, elicit the remodeling of vimentin filaments into small particles. Oxidative stress elicited by diamide induces a fast dissociation of filaments into circular, motile dots, which requires the presence of the single vimentin cysteine residue, C328. This effect is reversible, and filament reassembly can occur within minutes of oxidant removal. Diamide-elicited vimentin droplets recover fluorescence after photobleaching. Moreover, fusion of cells expressing differentially tagged vimentin allows the detection of dots positive for both tags, indicating that vimentin dots merge upon cell fusion. The aliphatic alcohol 1,6-hexanediol, known to alter interactions between low complexity domains, readily dissolves diamide-elicited vimentin dots at low concentrations, in a C328 dependent manner, and hampers reassembly. Taken together, these results indicate that vimentin oxidation promotes a fast and reversible filament remodeling into biomolecular condensate-like structures, and provide primary evidence of its regulated phase separation. Moreover, we hypothesize that filament to droplet transition could play a protective role against irreversible damage of the vimentin network by oxidative stress. Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. (Copyright © 2024 Agencia Estatal Consejo Superior de Investigaciones Científicas. Published by Elsevier B.V. All rights reserved.)
Databáze:	MEDLINE
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