{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"bioRxiv"}],"indexed":{"date-parts":[[2026,9,10]],"date-time":"2026-09-10T12:00:14Z","timestamp":1789041614507,"version":"build-2803163510"},"posted":{"date-parts":[[2025,5,28]]},"group-title":"Cell Biology","reference-count":74,"publisher":"openRxiv","license":[{"start":{"date-parts":[[2025,5,28]],"date-time":"2025-05-28T00:00:00Z","timestamp":1748390400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000057","name":"National Institute of General Medical Sciences","doi-asserted-by":"crossref","award":["R35GM129294"],"award-info":[{"award-number":["R35GM129294"]}],"id":[{"id":"10.13039\/100000057","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100000057","name":"National Institute of General Medical Sciences","doi-asserted-by":"crossref","award":["3R21CA280500-01A1S1"],"award-info":[{"award-number":["3R21CA280500-01A1S1"]}],"id":[{"id":"10.13039\/100000057","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100000057","name":"National Institute of General Medical Sciences","doi-asserted-by":"crossref","award":["T32AI055449-17"],"award-info":[{"award-number":["T32AI055449-17"]}],"id":[{"id":"10.13039\/100000057","id-type":"DOI","asserted-by":"crossref"}]},{"award":["Summer Fellowships"],"award-info":[{"award-number":["Summer Fellowships"]}],"id":[{"id":"https:\/\/ror.org\/008zs3103","id-type":"ROR","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2026,5,19]]},"abstract":"<jats:title>Text Abstract<\/jats:title>\n                <jats:p>\n                  In response to constant homeostatic threats, organisms have developed complex regulatory networks to monitor cellular functions and restore normal function. Here, we identify MDT-15 and its effectors, the fatty acid desaturases FAT-5, FAT-6, and FAT-7, as activators of the Ethanol and Stress Response (ESRE) mitochondrial surveillance pathway. Our data show that box C\/D snoRNPs, which were previously linked to ESRE activation, also regulate FAT-6 and FAT-7 protein levels. Notably, knockdown of\n                  <jats:italic>mdt-15<\/jats:italic>\n                  or\n                  <jats:italic>fib-1<\/jats:italic>\n                  , a component of box C\/D snoRNP complex, increased accumulation of the mitophagic activator PINK-1, the first step in licensing mitophagy, suggesting a relationship between ESRE surveillance and mitophagic activation. Supplementation with downstream unsaturated fatty acid products of FAT-6 and FAT-7 enhanced ESRE and mitophagic activation, but did not affect UPR\n                  <jats:sup>mt<\/jats:sup>\n                  . Since fatty acids activated ESRE and PINK-1 in wild-type and mutant genetic backgrounds, they are likely to act via a mechanism independent of FAT-6 and FAT-7 function. Our results provide insight into a novel interplay between box C\/D snoRNPs, MDT-15, and fatty acids in the regulation of mitochondrial surveillance and mitophagy.\n                <\/jats:p>\n                <jats:sec>\n                  <jats:title>Graphical Abstract<\/jats:title>\n                  <jats:fig id=\"ufig1\" position=\"float\" orientation=\"portrait\" fig-type=\"figure\">\n                    <jats:graphic xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" xlink:href=\"656193v2_ufig1\" position=\"float\" orientation=\"portrait\"\/>\n                  <\/jats:fig>\n                <\/jats:sec>","DOI":"10.1101\/2025.05.26.656193","type":"posted-content","created":{"date-parts":[[2025,5,28]],"date-time":"2025-05-28T05:55:16Z","timestamp":1748411716000},"source":"Crossref","is-referenced-by-count":4,"title":["Box C\/D snoRNPs and MDT-15\/MED15 regulate mitochondrial surveillance and mitophagy via fatty acid metabolism"],"prefix":"10.64898","author":[{"given":"Lois","family":"Armendariz","sequence":"first","affiliation":[{"name":"Department of BioSciences, Rice University, 6100 Main St, MS140, Houston, TX, 77005, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alicia","family":"Chan","sequence":"additional","affiliation":[{"name":"Department of BioSciences, Rice University, 6100 Main St, MS140, Houston, TX, 77005, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elissa","family":"Tjahjono","sequence":"additional","affiliation":[{"name":"Department of BioSciences, Rice University, 6100 Main St, MS140, Houston, TX, 77005, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Meggie","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of BioSciences, Rice University, 6100 Main St, MS140, Houston, TX, 77005, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yvette","family":"Acevedo","sequence":"additional","affiliation":[{"name":"Department of BioSciences, Rice University, 6100 Main St, MS140, Houston, TX, 77005, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1537-4967","authenticated-orcid":false,"given":"Natalia V.","family":"Kirienko","sequence":"additional","affiliation":[{"name":"Department of BioSciences, Rice University, 6100 Main St, MS140, Houston, TX, 77005, 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