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To test the interactive effects of food and temperature on the proteomic response to heat shock, the intertidal mussel Mytilus californianus was acclimated to four combinations of nearshore (low) and aquaculture (high) phytoplankton levels, combined with low (20\u00b0C) and high (30\u00b0C) aerial temperatures during daytime low tides. Whole mussels were then exposed to an acute (6\u2005h), aerial heat stress (33\u00b0C) and allowed to recover for 1 and 25\u2005h in pre-exposure conditions. Proteomic changes in the gill before and after heat shock were measured using liquid chromatography\u2013mass spectrometry and label-free quantification. Mussels acclimated to low temperature\u2013low food elicited a greater heat shock response compared with other acclimation groups, increasing protein levels of core carbohydrate and sulfide metabolism. These glycolytic metabolites proposedly feed into one-carbon metabolism (e.g. folate and methionine cycles) and connecting pathways, which also increased abundance and likely contribute to purine synthesis, methylation and transsulfuration. These mussels additionally increased levels of proteins scavenging hydrogen peroxide, chelating ferrous iron and maintaining reduced glutathione levels. Proteins modifying chromatin (histone) structure and regulating transcription likely link the metabolic changes to chromatin modifications, specifically through S-adenosylmethionine-dependent methyltransferases, which may contribute to repairing DNA damage caused by oxidative stress. Overall, our results suggest a food-dependent link between metabolism and epigenetic modifications that we hypothesize may function as an autoregulatory feedback mechanism during the cellular stress response under tidally fluctuating conditions.<\/jats:p>","DOI":"10.1242\/jeb.252105","type":"journal-article","created":{"date-parts":[[2026,7,14]],"date-time":"2026-07-14T09:36:17Z","timestamp":1784021777000},"source":"Crossref","is-referenced-by-count":2,"title":["Food-dependent activation of one-carbon metabolism during heat shock in\n                    <i>Mytilus californianus<\/i>"],"prefix":"10.1242","volume":"229","author":[{"ORCID":"https:\/\/orcid.org\/0009-0001-0555-9597","authenticated-orcid":false,"given":"R. Frank","family":"Fabela","sequence":"first","affiliation":[{"name":"California Polytechnic State University 1 , Department of Biological Sciences, 1 Grand Ave., San Luis Obispo, CA 93407 ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3235-8475","authenticated-orcid":false,"given":"Melissa A.","family":"May","sequence":"additional","affiliation":[{"name":"California Polytechnic State University 1 , Department of Biological Sciences, 1 Grand Ave., San Luis Obispo, CA 93407 ,","place":["USA"]},{"name":"Florida Gulf Coast University 2 , Department of Marine and Earth Sciences, 10501 FGCU Blvd. S, Fort Myers, FL 33965 ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9188-8038","authenticated-orcid":false,"given":"Lars","family":"Tomanek","sequence":"additional","affiliation":[{"name":"California Polytechnic State University 1 , Department of Biological Sciences, 1 Grand Ave., San Luis Obispo, CA 93407 ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"237","published-online":{"date-parts":[[2026,8,11]]},"reference":[{"key":"2026081103410570100_JEB252105C1","doi-asserted-by":"publisher","first-page":"556","DOI":"10.1038\/s41419-024-06939-5","article-title":"Oxidative cell death in cancer: mechanisms and therapeutic opportunities","volume":"15","author":"An","year":"2024","journal-title":"Cell Death Dis."},{"key":"2026081103410570100_JEB252105C2","volume-title":"Biology of Oysters","author":"Bayne","year":"2017"},{"key":"2026081103410570100_JEB252105C3","doi-asserted-by":"publisher","first-page":"289","DOI":"10.1111\/j.2517-6161.1995.tb02031.x","article-title":"Controlling for false discovery rate: a practical and powerful approach for multiple testing","volume":"57","author":"Benjamini","year":"1995","journal-title":"J. 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