{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,23]],"date-time":"2026-10-23T19:44:27Z","timestamp":1792784667309,"version":"4.5.0"},"reference-count":41,"publisher":"American Chemical Society (ACS)","issue":"10","license":[{"start":{"date-parts":[[2026,9,28]],"date-time":"2026-09-28T00:00:00Z","timestamp":1790553600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100000196","name":"Canada Foundation for Innovation","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100000196","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000057","name":"National Institute of General Medical Sciences","doi-asserted-by":"publisher","award":["R01GM122923"],"award-info":[{"award-number":["R01GM122923"]}],"id":[{"id":"10.13039\/100000057","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100013873","name":"Government of Ontario","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100013873","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Natural Sciences and Engineering Research Council of Canada (NSERC)","award":["RGPIN-2022-05058"],"award-info":[{"award-number":["RGPIN-2022-05058"]}],"id":[{"id":"https:\/\/ror.org\/01h531d29","id-type":"ROR","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2026,10,16]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Most inhibitors of lipid peroxidation (LPO) and associated ferroptosis are small molecules that trap LPO-propagating radicals. Among the handful of other inhibitors are select fatty acids: monounsaturated fatty acids (MUFAs) and polyunsaturated fatty acids substituted with deuterium atoms at their reactive bis-allylic positions (D-PUFAs), which render them significantly less reactive to LPO-propagating radicals. To probe whether the simple replacement of oxidizable PUFAs with non-oxidizable FAs is a general strategy for ferroptosis suppression, we prepared derivatives of representative PUFAs\u2014linoleic acid (LA) and arachidonic acid (AA)\u2014with cyclopropane rings in place of their unsaturations (CP-PUFAs). Cyclopropanation was predicted to boost the strength of the neighboring C\u2013H bonds by \u223c20 kcal\/mol and increase the barrier to reaction with peroxyl radicals by \u223c104-fold while preserving their cis geometry. CP-PUFAs suppressed ferroptosis induced by erastin2 in HT-1080 cells and RSL3 in HEK-293 cells, similarly to D-PUFAs and MUFAs. Palmitate, a representative endogenous saturated FA, did not suppress ferroptosis. Whereas d6-AA was more effective than d2-LA, the opposite was true of the CP-PUFAs, with CP4-AA possessing only modest activity while CP2-LA was comparable to the D-PUFAs. Lipidomics provides evidence for more extensive lipid remodeling upon treatment with CP2-LA relative to CP4-AA, with PUFAs being enriched in triacylglycerols at the expense of the diacylglycerols used for phospholipid synthesis. Overall, these results suggest that replacement of oxidizable PUFAs with non-oxidizable FAs is a general strategy to suppress ferroptosis\u2014provided that the non-oxidizable FA can be utilized by the biosynthetic machinery and is not lipotoxic at concentrations necessary for protection.<\/jats:p>","DOI":"10.1021\/acschembio.6c00583","type":"journal-article","created":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T00:02:03Z","timestamp":1790640123000},"page":"2702-2711","source":"Crossref","is-referenced-by-count":0,"title":["On the Inhibition of Lipid Peroxidation and Ferroptosis by Fatty Acids"],"prefix":"10.1021","volume":"21","author":[{"given":"Melodie","family":"Mallais","sequence":"first","affiliation":[{"name":"University of Ottawa , , , ,","place":["Ottawa, ON, Canada, K1N 6N5"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Krystina","family":"Szylo","sequence":"additional","affiliation":[{"name":"Stanford University , , , ,","place":["Stanford, California, United States, 94305"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Leslie","family":"Magtanong","sequence":"additional","affiliation":[{"name":"Stanford University , , , ,","place":["Stanford, California, United States, 94305"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mikhail S.","family":"Shchepinov","sequence":"additional","affiliation":[{"name":"\u00c9cole Nationale Sup\u00e9rieure De Chimie De Montpellier , , ,","place":["Montpellier, 34296, France"]},{"name":"University of Pittsburgh , , , ,","place":["Pittsburgh, Pennsylvania, United States, 15260"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6230-8199","authenticated-orcid":true,"given":"Scott J.","family":"Dixon","sequence":"additional","affiliation":[{"name":"Stanford University , , , ,","place":["Stanford, California, United States, 94305"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7305-745X","authenticated-orcid":true,"given":"Derek A.","family":"Pratt","sequence":"additional","affiliation":[{"name":"University of Ottawa , , , ,","place":["Ottawa, ON, Canada, K1N 6N5"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"316","published-online":{"date-parts":[[2026,9,28]]},"reference":[{"issue":"5","key":"2026101523064038100_cit1","doi-asserted-by":"publisher","first-page":"1060","DOI":"10.1016\/j.cell.2012.03.042","article-title":"Ferroptosis: An Iron-Dependent Form of Nonapoptotic Cell Death","volume":"149","author":"Dixon","year":"2012","journal-title":"Cell"},{"issue":"10","key":"2026101523064038100_cit2","doi-asserted-by":"publisher","first-page":"5944","DOI":"10.1021\/cr200084z","article-title":"Free Radical Lipid Peroxidation: Mechanisms and Analysis","volume":"111","author":"Yin","year":"2011","journal-title":"Chem. 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