A lower affinity to cytosolic proteins reveals VDAC3 isoform-specific role in mitochondrial biology

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dc.contributor.authorQueralt-Martín, María
dc.contributor.authorBergdoll, Lucie
dc.contributor.authorTeijido Hermida, Óscar
dc.contributor.authorMunshi, Nabill
dc.contributor.authorJacobs, Daniel
dc.contributor.authorKuszak, Adam J.
dc.contributor.authorProtchenko, Olga
dc.contributor.authorReina, Simona
dc.contributor.authorMagrì, Andrea
dc.contributor.authorDe Pinto, Vito
dc.contributor.authorBezrukov, Sergey M.
dc.contributor.authorAbramson, Jeff
dc.contributor.authorRostovtseva, Tatiana K.
dc.contributor.departmentCiencias de la Saludes_ES
dc.contributor.departmentOsasun Zientziakeu
dc.date.accessioned2025-04-01T08:02:37Z
dc.date.available2025-04-01T08:02:37Z
dc.date.issued2020-01-14
dc.date.updated2025-04-01T07:54:14Z
dc.description.abstractVoltage-dependent anion channel (VDAC) is the major pathway for the transport of ions and metabolites across the mitochondrial outer membrane. Among the three known mammalian VDAC isoforms, VDAC3 is the least characterized, but unique functional roles have been proposed in cellular and animal models. Yet, a high-sequence similarity between VDAC1 and VDAC3 is indicative of a similar pore-forming structure. Here, we conclusively show that VDAC3 forms stable, highly conductive voltage-gated channels that, much like VDAC1, are weakly anion selective and facilitate metabolite exchange, but exhibit unique properties when interacting with the cytosolic proteins α-synuclein and tubulin. These two proteins are knowntobepotent regulators of VDAC1 andinduce similar characteristic blockages (on the millisecond time scale) of VDAC3, but with 10- to 100-fold reduced on-rates and altered α-synuclein blocking times, indicative of an isoform-specific function. Through cysteine scanning mutagenesis, we found that VDAC3’s cysteine residues regulate its interaction with α-synuclein, demonstrating VDAC3-unique functional properties and further highlighting a general molecular mechanism for VDAC isoform-specific regulation of mitochondrial bioenergetics.en
dc.description.sponsorshipM. Queralt-Martín, D. Jacobs, S.M. Bezrukov, and T.K. Rostovtseva were supported by the Intramural Research Program of the National Institutes of Health, Eunice Kennedy Shriver National Institute of Child Health and Human Development. L. Bergdoll, N. Munshi, and J. Abramson were supported by National Institutes of Health R01GM078844 and the University of California, Los Angeles Cardiovascular Theme Discovery Award. V. De Pinto acknowledges the financial support by Ministero dell’Istruzione, dell’Università e della Ricerca (PRIN 2015795S5W_005).
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dc.format.mimetypeapplication/msworden
dc.identifier.citationQueralt-Martín, M., Bergdoll, L., Teijido, O., Munshi, N., Jacobs, D., Kuszak, A. J., Protchenko, O., Reina, S., Magrì, A., De Pinto, V., Bezrukov, S. M., Abramson, J., Rostovtseva, T. K. (2020). A lower affinity to cytosolic proteins reveals VDAC3 isoform-specific role in mitochondrial biology. Journal of General Physiology, 152(2), 1-13. https://doi.org/10.1085/jgp.201912501.
dc.identifier.doi10.1085/jgp.201912501
dc.identifier.issn0022-1295
dc.identifier.urihttps://academica-e.unavarra.es/handle/2454/53872
dc.language.isoeng
dc.publisherRockefeller University Press
dc.relation.ispartofJournal of General Physiology (2020), vol. 152, núm. 2, e201912501
dc.relation.publisherversionhttps://doi.org/10.1085/jgp.201912501
dc.rights© 2019 Queralt-Martín et al. This article is distributed under the terms of a Creative Commons License (Attribution-Noncommercial-Share Alike 4.0 International license.
dc.rights.accessRightsinfo:eu-repo/semantics/openAccess
dc.rights.urihttps://creativecommons.org/licenses/by-nc-sa/4.0/
dc.subjectBiophysicsen
dc.subjectMembrane transporten
dc.subjectMolecular physiologyen
dc.titleA lower affinity to cytosolic proteins reveals VDAC3 isoform-specific role in mitochondrial biologyen
dc.typeinfo:eu-repo/semantics/article
dc.type.versioninfo:eu-repo/semantics/publishedVersion
dspace.entity.typePublication
relation.isAuthorOfPublication2af87636-fad2-48e3-b5f6-f4a704d93613
relation.isAuthorOfPublication.latestForDiscovery2af87636-fad2-48e3-b5f6-f4a704d93613

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