{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,2]],"date-time":"2026-01-02T17:16:53Z","timestamp":1767374213998,"version":"build-2065373602"},"reference-count":69,"publisher":"MDPI AG","issue":"7","license":[{"start":{"date-parts":[[2022,4,1]],"date-time":"2022-04-01T00:00:00Z","timestamp":1648771200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"MCINN\/AEI\/ 10.13039\/501100011033","award":["PGC2018-093920-B-I00"],"award-info":[{"award-number":["PGC2018-093920-B-I00"]}]},{"DOI":"10.13039\/501100002809","name":"Generalitat de Catalunya","doi-asserted-by":"publisher","award":["2017-SGR-539","ICREA Academia"],"award-info":[{"award-number":["2017-SGR-539","ICREA Academia"]}],"id":[{"id":"10.13039\/501100002809","id-type":"DOI","asserted-by":"publisher"}]},{"name":"MCIN\/AEI \/10.13039\/501100011033","award":["CEX2018-000792-M Maria de Maeztu"],"award-info":[{"award-number":["CEX2018-000792-M Maria de Maeztu"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Many neurodegenerative disorders display protein aggregation as a hallmark, Huntingtin and TDP-43 aggregates being characteristic of Huntington disease and amyotrophic lateral sclerosis, respectively. However, whether these aggregates cause the diseases, are secondary by-products, or even have protective effects, is a matter of debate. Mutations in both human proteins can modulate the structure, number and type of aggregates, as well as their toxicity. To study the role of protein aggregates in cellular fitness, we have expressed in a highly tractable unicellular model different variants of Huntingtin and TDP-43. They each display specific patterns of aggregation and toxicity, even though in both cases proteins have to be very highly expressed to affect cell fitness. The aggregation properties of Huntingtin, but not of TDP-43, are affected by chaperones such as Hsp104 and the Hsp40 couple Mas5, suggesting that the TDP-43, but not Huntingtin, derivatives have intrinsic aggregation propensity. Importantly, expression of the aggregating form of Huntingtin causes a significant extension of fission yeast lifespan, probably as a consequence of kidnapping chaperones required for maintaining stress responses off. Our study demonstrates that in general these prion-like proteins do not cause toxicity under normal conditions, and in fact they can protect cells through indirect mechanisms which up-regulate cellular defense pathways.<\/jats:p>","DOI":"10.3390\/ijms23073950","type":"journal-article","created":{"date-parts":[[2022,4,1]],"date-time":"2022-04-01T21:22:39Z","timestamp":1648848159000},"page":"3950","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Expression of Huntingtin and TDP-43 Derivatives in Fission Yeast Can Cause Both Beneficial and Toxic Effects"],"prefix":"10.3390","volume":"23","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4777-5554","authenticated-orcid":false,"given":"Luis","family":"Marte","sequence":"first","affiliation":[{"name":"Oxidative Stress and Cell Cycle Group, Universitat Pompeu Fabra, C\/Doctor Aiguader 88, 08003 Barcelona, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1745-1556","authenticated-orcid":false,"given":"Susanna","family":"Boronat","sequence":"additional","affiliation":[{"name":"Oxidative Stress and Cell Cycle Group, Universitat Pompeu Fabra, C\/Doctor Aiguader 88, 08003 Barcelona, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4036-4960","authenticated-orcid":false,"given":"Rub\u00e9n","family":"Barrios","sequence":"additional","affiliation":[{"name":"Oxidative Stress and Cell Cycle Group, Universitat Pompeu Fabra, C\/Doctor Aiguader 88, 08003 Barcelona, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3487-1421","authenticated-orcid":false,"given":"Anna","family":"Barcons-Simon","sequence":"additional","affiliation":[{"name":"Oxidative Stress and Cell Cycle Group, Universitat Pompeu Fabra, C\/Doctor Aiguader 88, 08003 Barcelona, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Benedetta","family":"Bolognesi","sequence":"additional","affiliation":[{"name":"Institute of Bioengineering of Catalonia (IBEC), Baldiri Reixac 10\u201312, 08028 Barcelona, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Margarita","family":"Cabrera","sequence":"additional","affiliation":[{"name":"Oxidative Stress and Cell Cycle Group, Universitat Pompeu Fabra, C\/Doctor Aiguader 88, 08003 Barcelona, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6354-0536","authenticated-orcid":false,"given":"Jos\u00e9","family":"Ayt\u00e9","sequence":"additional","affiliation":[{"name":"Oxidative Stress and Cell Cycle Group, Universitat Pompeu Fabra, C\/Doctor Aiguader 88, 08003 Barcelona, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3768-6785","authenticated-orcid":false,"given":"Elena","family":"Hidalgo","sequence":"additional","affiliation":[{"name":"Oxidative Stress and Cell Cycle Group, Universitat Pompeu Fabra, C\/Doctor Aiguader 88, 08003 Barcelona, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2022,4,1]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"285","DOI":"10.1016\/j.tibs.2018.02.003","article-title":"Protein Disaggregation in Multicellular Organisms","volume":"43","author":"Nillegoda","year":"2018","journal-title":"Trends Biochem. 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