{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"bioRxiv"}],"indexed":{"date-parts":[[2026,6,24]],"date-time":"2026-06-24T06:01:30Z","timestamp":1782280890501,"version":"3.54.5"},"posted":{"date-parts":[[2025,6,18]]},"group-title":"Neuroscience","reference-count":47,"publisher":"openRxiv","license":[{"start":{"date-parts":[[2025,6,18]],"date-time":"2025-06-18T00:00:00Z","timestamp":1750204800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100000925","name":"National Health and Medical Research Council","doi-asserted-by":"crossref","award":["GNT1137645"],"award-info":[{"award-number":["GNT1137645"]}],"id":[{"id":"10.13039\/501100000925","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100000925","name":"National Health and Medical Research Council","doi-asserted-by":"crossref","award":["GNT2000766"],"award-info":[{"award-number":["GNT2000766"]}],"id":[{"id":"10.13039\/501100000925","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2025,6,18]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                <jats:p>\n                  Animals integrate environmental and internal cues to maintain homeostasis and health. The mitochondrial stress response is an essential cytoprotective mechanism, and priming its activation provides a survival advantage. Here, we show that the\n                  <jats:italic>Caenorhabditis elegans<\/jats:italic>\n                  receptor guanylyl cyclase GCY-9 regulates neuropeptide signalling from carbon dioxide sensing neurons to govern a non-canonical mitochondrial stress response in the intestine. This stress response induces atypical mitochondrial chaperone transcription, confers mitochondrial stress resistance, and increases mitochondrial membrane potential and respiration. GCY-9 loss disrupts pathogen avoidance, leading to indiscriminate feeding. We show that starvation decreases GCY-9 expression and propose that the resultant cytoprotective program is launched to offset risks associated with this behaviour. Thus, environmental sensing by peripheral neurons can pre-emptively enhance systemic mitochondrial function in response to metabolic uncertainty.\n                <\/jats:p>\n                <jats:sec>\n                  <jats:title>One-Sentence Summary<\/jats:title>\n                  <jats:p>Protecting mitochondria by integrating environmental signals<\/jats:p>\n                <\/jats:sec>","DOI":"10.1101\/2025.06.18.660458","type":"posted-content","created":{"date-parts":[[2025,6,19]],"date-time":"2025-06-19T00:50:11Z","timestamp":1750294211000},"source":"Crossref","is-referenced-by-count":0,"title":["Gas-sensing neurons prime mitochondrial fitness to offset metabolic stress"],"prefix":"10.64898","author":[{"given":"Rebecca","family":"Cornell","sequence":"first","affiliation":[{"name":"Development and Stem Cells Program, Monash Biomedicine Discovery Institute and Department of Anatomy and Developmental Biology, Monash University, Melbourne, Victoria 3800, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ava","family":"Handley","sequence":"additional","affiliation":[{"name":"Development and Stem Cells Program, Monash Biomedicine Discovery Institute and Department of Anatomy and Developmental Biology, Monash University, Melbourne, Victoria 3800, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5515-3608","authenticated-orcid":false,"given":"Roger","family":"Pocock","sequence":"additional","affiliation":[{"name":"Development and Stem Cells Program, Monash Biomedicine Discovery Institute and Department of Anatomy and Developmental Biology, Monash University, Melbourne, Victoria 3800, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"54368","reference":[{"key":"2026041204153754000_2025.06.18.660458v1.1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2016.08.042"},{"key":"2026041204153754000_2025.06.18.660458v1.2","doi-asserted-by":"publisher","DOI":"10.1038\/cr.2016.118"},{"key":"2026041204153754000_2025.06.18.660458v1.3","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2018.06.029"},{"key":"2026041204153754000_2025.06.18.660458v1.4","doi-asserted-by":"publisher","DOI":"10.1038\/s43587-023-00467-1"},{"key":"2026041204153754000_2025.06.18.660458v1.5","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-024-50973-y"},{"key":"2026041204153754000_2025.06.18.660458v1.6","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1017354108"},{"key":"2026041204153754000_2025.06.18.660458v1.7","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1610673114"},{"key":"2026041204153754000_2025.06.18.660458v1.8","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pbio.3001655"},{"key":"2026041204153754000_2025.06.18.660458v1.9","doi-asserted-by":"publisher","DOI":"10.1534\/genetics.111.133835"},{"key":"2026041204153754000_2025.06.18.660458v1.10","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0034014"},{"key":"2026041204153754000_2025.06.18.660458v1.11","doi-asserted-by":"publisher","DOI":"10.1534\/genetics.106.061580"},{"key":"2026041204153754000_2025.06.18.660458v1.12","doi-asserted-by":"crossref","unstructured":"C. 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