{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T10:19:56Z","timestamp":1785406796128,"version":"3.56.0"},"reference-count":47,"publisher":"Life Science Alliance, LLC","issue":"6","license":[{"start":{"date-parts":[[2026,4,17]],"date-time":"2026-04-17T00:00:00Z","timestamp":1776384000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100014440","name":"Ministerio de Ciencia, Innovaci\u00f3n y Universidades","doi-asserted-by":"publisher","award":["RYC2022-035365-I"],"award-info":[{"award-number":["RYC2022-035365-I"]}],"id":[{"id":"10.13039\/100014440","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100004440","name":"Wellcome","doi-asserted-by":"publisher","award":["224407\/Z\/21Z"],"award-info":[{"award-number":["224407\/Z\/21Z"]}],"id":[{"id":"10.13039\/100004440","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["life-science-alliance.org"],"crossmark-restriction":true},"short-container-title":["Life Sci. Alliance"],"accepted":{"date-parts":[[2026,3,27]]},"published-print":{"date-parts":[[2026,6]]},"abstract":"<jats:p>\n                    The transcription factor ATF6\u03b1 has a central role in adapting mammalian cells to ER stress via the unfolded protein response (UPR), prompting efforts to identify ATF6\u03b1 modulators. Here, an unbiased genome-wide CRISPR-Cas9 screen performed in Chinese Hamster Ovary cells revealed that proteolytic processing of the ATF6\u03b1 precursor to its active form was impaired in cells lacking the ER-resident solute carrier SLC33A1, a transporter previously implicated in acetyl-CoA import, sialylation, and N\u03b5-lysine protein acetylation. Cells lacking SLC33A1 constitutively trafficked the ATF6\u03b1 to the Golgi but exhibited impaired Golgi processing and activating proteolysis. IRE1\u03b1 signalling was derepressed by SLC33A1 deficiency consistent with selective loss of ATF6\u03b1-mediated negative feedback in the UPR.\n                    <jats:italic>Slc33a1<\/jats:italic>\n                    -deleted cells accumulated unmodified sialylated N-glycans, precursors to acetylated glycans, likely reflecting impaired glycan processing. Deletion of ER-localised acetyltransferases NAT8 and NAT8B, which catalyse protein N\u03b5-lysine acetylation in the secretory pathway, did not replicate the ATF6\u03b1 processing defects observed in\n                    <jats:italic>Slc33a1<\/jats:italic>\n                    -deficient cells. Together, our findings highlight a role of SLC33A1-mediated metabolite transport in the post-ER ATF6\u03b1 maturation, linking small-molecule metabolism to branch-specific signalling in the UPR.\n                  <\/jats:p>","DOI":"10.26508\/lsa.202603679","type":"journal-article","created":{"date-parts":[[2026,4,17]],"date-time":"2026-04-17T19:10:19Z","timestamp":1776453019000},"page":"e202603679","update-policy":"https:\/\/doi.org\/10.26508\/lsa.crossmarkpolicy","source":"Crossref","is-referenced-by-count":0,"title":["Metabolite import by SLC33A1 is required for ATF6 activation during endoplasmic reticulum stress"],"prefix":"10.26508","volume":"9","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-4804-9594","authenticated-orcid":true,"given":"Ginto","family":"George","sequence":"first","affiliation":[{"id":[{"id":"https:\/\/ror.org\/013meh722","id-type":"ROR","asserted-by":"publisher"}],"name":"Cambridge Institute for Medical Research (CIMR), University of Cambridge","place":[", 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