A mathematical model of p62-ubiquitin aggregates in autophagy

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• dc.contributor.author Delacour, Julia
• dc.contributor.author Doumic, Marie
• dc.contributor.author Martens, Sascha
• dc.contributor.author Schmeiser, Christian
• dc.contributor.author Zaffagnini, Gabriele
• dc.date.accessioned 2022-03-25T07:06:08Z
• dc.date.available 2022-03-25T07:06:08Z
• dc.date.issued 2021
• dc.description.abstract Aggregation of ubiquitinated cargo by oligomers of the protein p62 is an important preparatory step in cellular autophagy. In this work a mathematical model for the dynamics of these heterogeneous aggregates in the form of a system of ordinary differential equations is derived and analyzed. Three different parameter regimes are identified, where either aggregates are unstable, or their size saturates at a finite value, or their size grows indefinitely as long as free particles are abundant. The boundaries of these regimes as well as the finite size in the second case can be computed explicitly. The growth in the third case (quadratic in time) can also be made explicit by formal asymptotic methods. In the absence of rigorous results the dynamic stability of these structures has been investigated by numerical simulations. A comparison with recent experimental results permits a partial parametrization of the model.
• dc.description.sponsorship This work has been supported by the PhD program Signalling Mechanisms in Cellular Autophagy, funded by the Austrian Science Fund (FWF), project no. W1261. CS also acknowledges support by FWF, Grant Nos. W1245 and SFB65. MD and JD have been partially supported by the ERC Starting Grant SKIPPERAD (Number 306321). MD thanks the Wolfgang Pauli Institute for the sabbatical stay in Vienna during which this work has been initiated.
• dc.format.mimetype application/pdf
• dc.identifier.citation Delacour J, Doumic M, Martens S, Schmeiser C, Zaffagnini G. A mathematical model of p62-ubiquitin aggregates in autophagy. J Math Biol. 2021 Dec 14;84(1-2):3. DOI: 10.1007/s00285-021-01659-2
• dc.identifier.doi http://dx.doi.org/10.1007/s00285-021-01659-2
• dc.identifier.issn 0303-6812
• dc.identifier.uri http://hdl.handle.net/10230/52773
• dc.language.iso eng
• dc.publisher Springer
• dc.relation.ispartof J Math Biol. 2021 Dec 14;84(1-2):3
• dc.relation.projectID info:eu-repo/grantAgreement/EC/FP7/306321
• dc.rights © The Author(s) 2021. Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/.
• dc.rights.accessRights info:eu-repo/semantics/openAccess
• dc.rights.uri http://creativecommons.org/licenses/by/4.0/
• dc.subject.keyword 92C40 Biochemistry
• dc.subject.keyword Molecular biology
• dc.title A mathematical model of p62-ubiquitin aggregates in autophagy
• dc.type info:eu-repo/semantics/article
• dc.type.version info:eu-repo/semantics/publishedVersion