{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"bioRxiv"}],"indexed":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T13:00:35Z","timestamp":1785416435117,"version":"3.56.0"},"posted":{"date-parts":[[2025,11,10]]},"group-title":"Cell Biology","reference-count":53,"publisher":"openRxiv","license":[{"start":{"date-parts":[[2025,11,10]],"date-time":"2025-11-10T00:00:00Z","timestamp":1762732800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"award":["MCB 2127616"],"award-info":[{"award-number":["MCB 2127616"]}],"id":[{"id":"https:\/\/ror.org\/021nxhr62","id-type":"ROR","asserted-by":"publisher"}]},{"award":["MCB CAREER 1942395"],"award-info":[{"award-number":["MCB CAREER 1942395"]}],"id":[{"id":"https:\/\/ror.org\/021nxhr62","id-type":"ROR","asserted-by":"publisher"}]},{"award":["GM155860"],"award-info":[{"award-number":["GM155860"]}],"id":[{"id":"https:\/\/ror.org\/01cwqze88","id-type":"ROR","asserted-by":"publisher"}]},{"id":[{"id":"https:\/\/ror.org\/04gr4te78","id-type":"ROR","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2025,11,10]]},"abstract":"<jats:title>Summary<\/jats:title>\n                <jats:p>\n                  Stress granules are biomolecular condensates that form in response to environmental stress and disassemble once normal conditions are restored. However, when disassembly fails, stress granules can persist and solidify. While stress granule solidification has been well documented, the cellular mechanisms underlying the transition from reversible to persistent stress granules remain unclear. Persistent stress granules can seed the formation of pathological aggregates, such as TDP-43 in amyotrophic lateral sclerosis\n                  <jats:sup>1, 2<\/jats:sup>\n                  . Although amyloid and tau aggregates are hallmarks of Alzheimer\u2019s disease, a subset of patients also develop TDP-43 deposits, suggesting a possible role for stress granule solidification in Alzheimer\u2019s disease progression\n                  <jats:sup>3\u20135<\/jats:sup>\n                  . Despite theoretical models explaining why persistence and ensuing solidification occurs, strong\n                  <jats:italic>in vivo<\/jats:italic>\n                  evidence is lacking\n                  <jats:sup>6<\/jats:sup>\n                  . Here we show that competition for limited chaperone resources drive stress granule persistence. In the presence of TDP-43 aggregates or yeast amyloid proteins called prions, stress granule disassembly is slowed or halted disassembly. Using yeast prions as a model, we show that the addition of chaperones, specifically the AAA+ ATPase molecular chaperone, Hsp104, resulted in resumption of stress granule disassembly. Our results demonstrate that the competition for shared resources, such as molecular chaperones, can limit stress granule disassembly. We suspect that the presence of pathological aggregates results in resource competition within the aging brain, contributing to the persistence of stress granules and their subsequent solidification and aggregation.\n                <\/jats:p>","DOI":"10.1101\/2025.11.08.687377","type":"posted-content","created":{"date-parts":[[2025,11,10]],"date-time":"2025-11-10T21:40:10Z","timestamp":1762810810000},"source":"Crossref","is-referenced-by-count":2,"title":["Stress granules and protein aggregates reveal intracellular resource competition"],"prefix":"10.64898","author":[{"given":"Hannah E.","family":"Buchholz","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sean A.","family":"Martin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jane E.","family":"Dorweiler","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Derek C.","family":"Prosser","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Emily M.","family":"Sontag","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0844-1479","authenticated-orcid":false,"given":"Anita L.","family":"Manogaran","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"54368","reference":[{"key":"2025111204100754000_2025.11.08.687377v1.1","doi-asserted-by":"publisher","DOI":"10.1038\/s41580-020-00326-6"},{"key":"2025111204100754000_2025.11.08.687377v1.2","doi-asserted-by":"crossref","unstructured":"Yan, X. , et al. Intra-condensate demixing of TDP-43 inside stress granules generates pathological aggregates. Cell (2025).","DOI":"10.1101\/2024.01.23.576837"},{"key":"2025111204100754000_2025.11.08.687377v1.3","doi-asserted-by":"publisher","DOI":"10.1002\/ana.21154"},{"key":"2025111204100754000_2025.11.08.687377v1.4","doi-asserted-by":"publisher","DOI":"10.1007\/s00401-014-1269-z"},{"key":"2025111204100754000_2025.11.08.687377v1.5","doi-asserted-by":"publisher","DOI":"10.1016\/S1474-4422(17)30284-3"},{"key":"2025111204100754000_2025.11.08.687377v1.6","doi-asserted-by":"publisher","DOI":"10.1038\/s41593-018-0235-9"},{"key":"2025111204100754000_2025.11.08.687377v1.7","doi-asserted-by":"crossref","unstructured":"Buchan, J.R . Stress granule and P-body clearance: Seeking coherence in acts of disappearance. Semin Cell Dev Biol 159-160, 10-26 (2024).","DOI":"10.1016\/j.semcdb.2024.01.002"},{"key":"2025111204100754000_2025.11.08.687377v1.8","doi-asserted-by":"publisher","DOI":"10.1083\/jcb.201302044"},{"key":"2025111204100754000_2025.11.08.687377v1.9","doi-asserted-by":"crossref","unstructured":"Dudman, J. & Qi, X . Stress Granule Dysregulation in Amyotrophic Lateral Sclerosis. 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Distinct stages in stress granule assembly and disassembly. eLife 5 (2016).","DOI":"10.7554\/eLife.18413"},{"key":"2025111204100754000_2025.11.08.687377v1.22","doi-asserted-by":"publisher","DOI":"10.1038\/sj.emboj.7600426"},{"key":"2025111204100754000_2025.11.08.687377v1.23","doi-asserted-by":"publisher","DOI":"10.1016\/j.sbi.2009.11.001"},{"key":"2025111204100754000_2025.11.08.687377v1.24","doi-asserted-by":"publisher","DOI":"10.1371\/journal.ppat.1003537"},{"key":"2025111204100754000_2025.11.08.687377v1.25","doi-asserted-by":"crossref","unstructured":"Tilman, D . Resource competition and community structure . 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