{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"bioRxiv"}],"indexed":{"date-parts":[[2026,9,5]],"date-time":"2026-09-05T17:12:27Z","timestamp":1788628347453,"version":"build-2803163510"},"posted":{"date-parts":[[2026,9,2]]},"group-title":"Cell Biology","reference-count":46,"publisher":"openRxiv","license":[{"start":{"date-parts":[[2026,9,2]],"date-time":"2026-09-02T00:00:00Z","timestamp":1788307200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/www.biorxiv.org\/about\/FAQ#license"}],"funder":[{"award":["NIH P40OD018537"],"award-info":[{"award-number":["NIH P40OD018537"]}],"id":[{"id":"https:\/\/ror.org\/001d55x84","id-type":"ROR","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2026,9,2]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                <jats:p>\n                  MYC-driven metabolic reprogramming supports rapid cell growth but also creates metabolic demands that require adaptive mechanisms to maintain cellular homeostasis. Here, combining clonal analysis in\n                  <jats:italic>Drosophila<\/jats:italic>\n                  wing imaginal discs with studies in Schneider S2 cells, we identify glutamine metabolism as a component of Myc-induced autophagy. Myc increased the expression of genes involved in glutamine utilization, including glutaminase (GLS), and enhanced ammonia production, a metabolic by-product of glutaminolysis. Genetic depletion of GLS in clones suppressed the accumulation of Myc-induced Atg8a-positive structures and reduced autophagic flux, demonstrating that glutaminase contributes to the autophagic response elicited by Myc. Exogenous NH\u2084Cl was sufficient to induce Atg8a-positive structures and partially restored their accumulation following GLS depletion, supporting ammonia as a downstream contributor to this response. Mechanistically, Myc-induced autophagy in clones required the core autophagy factor Atg5 but was not suppressed by activation of Rheb\/TOR signaling or Atg1 depletion, indicating reduced dependence on canonical TOR-Atg1 regulation. We further found that Myc activity is required for Ras\n                  <jats:sup>V12<\/jats:sup>\n                  -driven epithelial overgrowth and that Ras\n                  <jats:sup>V12<\/jats:sup>\n                  cells induce a pronounced non-cell-autonomous accumulation of Atg8a-positive structures in wild-type cells surrounding Ras\n                  <jats:sup>V12<\/jats:sup>\n                  clones. Depletion of either Myc or Gls in Ras\n                  <jats:sup>V12<\/jats:sup>\n                  cells strongly reduced this neighboring autophagic response. Together, our findings identify Gls-dependent glutamine metabolism as a previously unrecognized component of Myc-induced autophagy and extend this relationship to Ras-transformed epithelia, linking the metabolic state of transformed cells to autophagy in the surrounding tissue.\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=\"748041v1_ufig1\" position=\"float\" orientation=\"portrait\"\/>\n                  <\/jats:fig>\n                  <jats:p>\n                    Myc increases glutaminase (Gls)-dependent glutamine catabolism, promoting ammonia production and Atg5-dependent autophagy in Drosophila epithelial cells. In Ras\n                    <jats:sup>V12-<\/jats:sup>\n                    transformed epithelia, Myc and Gls are also required for the induction of autophagy in neighboring wild-type cells, suggesting that metabolic signals generated by transformed cells can elicit a non-cell-autonomous autophagic response. Solid arrows indicate experimentally supported relationships, whereas the dashed arrow denotes a proposed metabolic signal whose identity remains to be established.\n                  <\/jats:p>\n                <\/jats:sec>","DOI":"10.64898\/2026.08.31.748041","type":"posted-content","created":{"date-parts":[[2026,9,3]],"date-time":"2026-09-03T07:15:10Z","timestamp":1788419710000},"source":"Crossref","is-referenced-by-count":0,"title":["Glutaminase contributes to MYC-induced cell-autonomous autophagy and to Ras\n                  <sup>V12<\/sup>\n                  -dependent non-autonomous autophagy in the Drosophila wing disc epithelium"],"prefix":"10.64898","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-2513-4622","authenticated-orcid":false,"given":"Francesca","family":"Destefanis","sequence":"first","affiliation":[{"name":"Department of Cellular, Computational and Integrative Biology (CIBIO), University of Trento, Trento, Italy"},{"name":"Botanical Institute of Barcelona (IBB-CSIC), Barcelona, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lorenzo","family":"Conci","sequence":"additional","affiliation":[{"name":"Department of Cellular, Computational and Integrative Biology (CIBIO), University of Trento, Trento, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0005-6229-3464","authenticated-orcid":false,"given":"Shivani","family":"Bajaj","sequence":"additional","affiliation":[{"name":"Department of Cellular, Computational and Integrative Biology (CIBIO), University of Trento, Trento, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9292-6588","authenticated-orcid":false,"given":"Valeria","family":"Manara","sequence":"additional","affiliation":[{"name":"Department of Cellular, Computational and Integrative Biology (CIBIO), University of Trento, Trento, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1913-5661","authenticated-orcid":false,"given":"Paola","family":"Bellosta","sequence":"additional","affiliation":[{"name":"Department of Cellular, Computational and Integrative Biology (CIBIO), University of Trento, Trento, Italy"},{"name":"Department of Medicine, New York University Grossman School of Medicine, New York, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"54368","reference":[{"issue":"4","key":"2026090509400946000_2026.08.31.748041v1.1","doi-asserted-by":"crossref","first-page":"189651","DOI":"10.1016\/j.bbcan.2026.189651","article-title":"The MYC network: Hub of malignancy and blueprint for intervention","volume":"1881","year":"2026","journal-title":"Biochim Biophys Acta Rev Cancer"},{"key":"2026090509400946000_2026.08.31.748041v1.2","doi-asserted-by":"publisher","DOI":"10.1158\/2159-8290.CD-15-0507"},{"key":"2026090509400946000_2026.08.31.748041v1.3","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0810199105"},{"key":"2026090509400946000_2026.08.31.748041v1.4","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0709747104"},{"key":"2026090509400946000_2026.08.31.748041v1.5","doi-asserted-by":"publisher","DOI":"10.1016\/j.tibs.2010.05.003"},{"key":"2026090509400946000_2026.08.31.748041v1.6","doi-asserted-by":"publisher","DOI":"10.1007\/978-3-319-42118-6_4"},{"key":"2026090509400946000_2026.08.31.748041v1.7","doi-asserted-by":"publisher","DOI":"10.1016\/j.ydbio.2013.04.008"},{"key":"2026090509400946000_2026.08.31.748041v1.8","doi-asserted-by":"crossref","unstructured":"C. de la Cova , N. 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