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Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[2025,11,25]]},"abstract":"<jats:p>\n                    <jats:italic toggle=\"yes\">BET1, GOSR2,<\/jats:italic>\n                    and\n                    <jats:italic toggle=\"yes\">STX5<\/jats:italic>\n                    variants can cause fatal inherited diseases, including epilepsies, muscular dystrophy, and multisystemic disorders. Together with Sec22b, they form a SNARE complex that mediates fusion of ER-derived vesicles with the ER-Golgi-intermediate compartment and the\n                    <jats:italic toggle=\"yes\">cis<\/jats:italic>\n                    -Golgi. The Sec1\/Munc18 protein SCFD1\/Sly1 accelerates ER-to-Golgi SNARE complex assembly and membrane fusion, but much less is known about downregulation of ER-to-Golgi trafficking under cellular stress conditions. Here, we identify the lactate and hypoxia sensor protein NDRG3 as a binding partner of the ER-to-Golgi SNARE complex. NDRG3 binds via its C-terminal domain to the N-terminal domain of the long isoform of Stx5, thereby impairing ER-to-Golgi trafficking under hypoxic conditions and elevated intracellular lactate levels. In NDRG3-deficient cells, hypoxia- and lactate-induced inhibition of ER-to-Golgi trafficking is abolished. Our work identifies NDRG3 as a negative regulator of ER-to-Golgi SNARE complex function, mechanistically linking hypoxia and lactate to membrane trafficking in the secretory pathway.\n                  <\/jats:p>","DOI":"10.1073\/pnas.2511307122","type":"journal-article","created":{"date-parts":[[2025,11,18]],"date-time":"2025-11-18T16:18:08Z","timestamp":1763482688000},"update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":1,"title":["The lactate sensor NDRG3 decelerates ER-to-Golgi transport through interaction with the long isoform of syntaxin-5"],"prefix":"10.1073","volume":"122","author":[{"ORCID":"https:\/\/orcid.org\/0009-0005-2598-0898","authenticated-orcid":false,"given":"Pia E.","family":"Ferle","sequence":"first","affiliation":[{"name":"Faculty of Chemistry, Biochemistry III (BCIII), University of Bielefeld","place":["Bielefeld, 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Biochemistry III (BCIII), University of Bielefeld","place":["Bielefeld, Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0515-655X","authenticated-orcid":false,"given":"Alexander","family":"Hillebrand","sequence":"additional","affiliation":[{"name":"Faculty of Chemistry, Biochemistry III (BCIII), University of Bielefeld","place":["Bielefeld, Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1064-6350","authenticated-orcid":false,"given":"Leonie F.","family":"Schr\u00f6der","sequence":"additional","affiliation":[{"name":"Faculty of Chemistry, Biochemistry III (BCIII), University of Bielefeld","place":["Bielefeld, Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stefanie","family":"J\u00e4ger","sequence":"additional","affiliation":[{"name":"Medical School Hamburg, University of Applied Sciences and Medical University","place":["Hamburg, 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