Mouse oocytes sequester aggregated proteins in degradative super-organelles
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- dc.contributor.author Zaffagnini, Gabriele
- dc.contributor.author Cheng, Shiya
- dc.contributor.author Salzer, Marion C.
- dc.contributor.author Pernaute, Barbara
- dc.contributor.author Duran, Juan M.
- dc.contributor.author Irimia Martínez, Manuel
- dc.contributor.author Schuh, Melina
- dc.contributor.author Böke, Elvan
- dc.date.accessioned 2024-07-23T06:37:45Z
- dc.date.available 2024-07-23T06:37:45Z
- dc.date.issued 2024
- dc.description.abstract Oocytes are among the longest-lived cells in the body and need to preserve their cytoplasm to support proper embryonic development. Protein aggregation is a major threat for intracellular homeostasis in long-lived cells. How oocytes cope with protein aggregation during their extended life is unknown. Here, we find that mouse oocytes accumulate protein aggregates in specialized compartments that we named endolysosomal vesicular assemblies (ELVAs). Combining live-cell imaging, electron microscopy, and proteomics, we found that ELVAs are non-membrane-bound compartments composed of endolysosomes, autophagosomes, and proteasomes held together by a protein matrix formed by RUFY1. Functional assays revealed that in immature oocytes, ELVAs sequester aggregated proteins, including TDP-43, and degrade them upon oocyte maturation. Inhibiting degradative activity in ELVAs leads to the accumulation of protein aggregates in the embryo and is detrimental for embryo survival. Thus, ELVAs represent a strategy to safeguard protein homeostasis in long-lived cells.
- dc.description.sponsorship We acknowledge the support of the Spanish Ministry of Science and Innovation through the Centro de Excelencia Severo Ochoa (CEX2020-001049-S, MCIN/AEI/10.13039/501100011033) and the Generalitat de Catalunya through the CERCA program. G.Z. received funding from the European Union’s Horizon 2020 research and innovation program under the Marie Skłodowska-Curie grant agreement no. 754422. E.B. acknowledges funding from the Ministerio de Ciencia e Innovación PID2020-115127GB-I00, the European Research Council Starting Grant (ERC-StG-2017-759107), and the Vallee Scholar Award (Vallee Foundation Inc.). The work of S.C. and M.S. was supported by the Max Planck Society and the Deutsche Forschungsgemeinschaft (DFG, German Research Foundation) under Germany’s Excellence Strategy (EXC 2067/1-390729940) and a DFG Leibniz Prize to M.S. (SCHU 3047/1-1). S.C. was additionally supported by a European Molecular Biology Organization long-term postdoctoral fellowship.
- dc.format.mimetype application/pdf
- dc.identifier.citation Zaffagnini G, Cheng S, Salzer MC, Pernaute B, Duran JM, Irimia M, et al. Mouse oocytes sequester aggregated proteins in degradative super-organelles. Cell. 2024 Feb 29;187(5):1109-26.e21. DOI: 10.1016/j.cell.2024.01.031
- dc.identifier.doi http://dx.doi.org/10.1016/j.cell.2024.01.031
- dc.identifier.issn 0092-8674
- dc.identifier.uri http://hdl.handle.net/10230/60808
- dc.language.iso eng
- dc.publisher Elsevier
- dc.relation.ispartof Cell. 2024 Feb 29;187(5):1109-26.e21
- dc.relation.projectID info:eu-repo/grantAgreement/EC/H2020/754422
- dc.relation.projectID info:eu-repo/grantAgreement/ES/2PE/PID2020-115127GB-I00
- dc.relation.projectID info:eu-repo/grantAgreement/EC/H2020/759107
- dc.rights © 2024 The Author(s). Published by Elsevier Inc. This is an open access article under the CC BY-NC license (http://creativecommons.org/licenses/by-nc/4.0/).
- dc.rights.accessRights info:eu-repo/semantics/openAccess
- dc.rights.uri http://creativecommons.org/licenses/by-nc/4.0/
- dc.subject.keyword RUFY1
- dc.subject.keyword Embryo
- dc.subject.keyword Female fertility
- dc.subject.keyword Lysosomal acidification
- dc.subject.keyword Membraneless organelles
- dc.subject.keyword Oocyte
- dc.subject.keyword Oocyte quality
- dc.subject.keyword Protein aggregation
- dc.subject.keyword Proteostasis
- dc.subject.keyword Super-organelles
- dc.title Mouse oocytes sequester aggregated proteins in degradative super-organelles
- dc.type info:eu-repo/semantics/article
- dc.type.version info:eu-repo/semantics/publishedVersion