{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"bioRxiv"}],"indexed":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T11:33:56Z","timestamp":1785411236714,"version":"3.56.0"},"posted":{"date-parts":[[2025,11,10]]},"group-title":"Cell Biology","reference-count":90,"publisher":"openRxiv","license":[{"start":{"date-parts":[[2025,11,10]],"date-time":"2025-11-10T00:00:00Z","timestamp":1762732800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"award":["R35NS132156"],"award-info":[{"award-number":["R35NS132156"]}],"id":[{"id":"https:\/\/ror.org\/001d55x84","id-type":"ROR","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2026,5,16]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                <jats:p>\n                  Tissues exhibit metabolic heterogeneity that tailors conserved pathways to distinct physiological demands, yet how this heterogeneity is achieved\n                  <jats:italic>in vivo<\/jats:italic>\n                  remains poorly understood. Here, we use\n                  <jats:italic>Caenorhabditis elegans<\/jats:italic>\n                  to investigate tissue-specific requirements for glucose-6-phosphate isomerase (GPI-1), a conserved reversible enzyme that links glycolysis and the pentose phosphate pathway (PPP). Tissue-specific metabolic-network modeling predicted differential glycolytic and PPP flux potential across adult tissues and identified tissue-specific biases in GPI-1 reaction directionality. Genetic disruption of\n                  <jats:italic>gpi-1<\/jats:italic>\n                  produced germline defects consistent with impaired PPP-associated anabolic metabolism and somatic defects consistent with impaired glycolysis, indicating that GPI-1 supports distinct metabolic functions across tissues. We further discovered that two GPI-1 isoforms are differentially expressed and localized: GPI-1A is broadly expressed and cytosolic, whereas GPI-1B is enriched in the germline and localizes to endoplasmic reticulum\u2013associated compartments. Isoform-specific perturbations revealed distinct requirements for GPI-1A and GPI-1B in somatic glycolysis and reproductive physiology. These findings implicate isoform-specific subcellular localization as a possible contributor to the partition of the functions of a conserved reversible enzyme, enabling tissue-specific anabolic and catabolic metabolism\n                  <jats:italic>in vivo<\/jats:italic>\n                  .\n                <\/jats:p>","DOI":"10.1101\/2025.11.09.687253","type":"posted-content","created":{"date-parts":[[2025,11,10]],"date-time":"2025-11-10T12:40:13Z","timestamp":1762778413000},"source":"Crossref","is-referenced-by-count":0,"title":["Spatial Partitioning of Glucose Metabolism Supports Tissue-Specific Metabolic Programs In Vivo"],"prefix":"10.64898","author":[{"given":"Ian J.","family":"Gonzalez","sequence":"first","affiliation":[{"name":"Department of Neuroscience and Department of Cell Biology, Yale University School of Medicine; New Haven, CT 06510, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aaron D.","family":"Wolfe","sequence":"additional","affiliation":[{"name":"Department of Neuroscience and Department of Cell Biology, Yale University School of Medicine; New Haven, CT 06510, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Benjamin","family":"Clark","sequence":"additional","affiliation":[{"name":"Department of Neuroscience and Department of Cell Biology, Yale University School of Medicine; New Haven, CT 06510, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael","family":"Hanna","sequence":"additional","affiliation":[{"name":"Department of Neuroscience and Department of Cell Biology, Yale University School of Medicine; New Haven, CT 06510, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gabrielle E.","family":"Geise","sequence":"additional","affiliation":[{"name":"Department of Systems Biology, University of Massachusetts Chan Medical School; Worcester, MA 01655, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Quishi","family":"Sun","sequence":"additional","affiliation":[{"name":"Department of Endocrinology, Yale University School of Medicine; New Haven, CT 06510, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Snusha","family":"Ravikumar","sequence":"additional","affiliation":[{"name":"Department of Neuroscience and Department of Cell Biology, Yale University School of Medicine; New Haven, CT 06510, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anastasia","family":"Tsives","sequence":"additional","affiliation":[{"name":"Department of Neuroscience and Department of Cell Biology, Yale University School of Medicine; New Haven, CT 06510, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sarah E.","family":"Emerson","sequence":"additional","affiliation":[{"name":"Department of Neuroscience and Department of Cell Biology, Yale University School of Medicine; New Haven, CT 06510, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stephan","family":"Siebel","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Yale University School of Medicine; New Haven, CT 06510, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Richard","family":"Kibbey","sequence":"additional","affiliation":[{"name":"Department of Endocrinology, Yale University School of Medicine; New Haven, CT 06510, USA"},{"name":"Department of Cellular and Molecular Physiology, Yale University School of Medicine; New Haven, CT 06510, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"L. Safak","family":"Yilmaz","sequence":"additional","affiliation":[{"name":"Department of Systems Biology, University of Massachusetts Chan Medical School; Worcester, MA 01655, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Albertha J.M.","family":"Walhout","sequence":"additional","affiliation":[{"name":"Department of Systems Biology, University of Massachusetts Chan Medical School; Worcester, MA 01655, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0223-7717","authenticated-orcid":false,"given":"Daniel","family":"Col\u00f3n-Ramos","sequence":"additional","affiliation":[{"name":"Department of Neuroscience and Department of Cell Biology, Yale University School of Medicine; New Haven, CT 06510, USA"},{"name":"Wu Tsai Institute, Yale University; New Haven, CT 06510, USA"},{"name":"Instituto de Neurobiolog\u00eda, Recinto de Ciencias M\u00e9dicas, Universidad de Puerto Rico, San Juan 00901, Puerto 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