p38 MAPK orchestrates cross-tissue potassium homeostasis for survival

p38 MAPK orchestrates cross-tissue potassium homeostasis for survival | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Article p38 MAPK orchestrates cross-tissue potassium homeostasis for survival Ziyun Wu, Fangchao Hu, Rong Huang, Qifei Gao, Yiyao Li, Jintao Huang, and 5 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-7350614/v1 This work is licensed under a CC BY 4.0 License Status: Published Journal Publication published 09 Mar, 2026 Read the published version in Nature Communications → Version 1 posted You are reading this latest preprint version Abstract Potassium is vital for life, yet how potassium homeostasis is maintained at the tissue or organismal level under dietary scarcity remains poorly understood. Stress-activated signaling pathway p38 MAPK is implicated in immune response and aging, but its roles in low potassium response is unclear. Here we show that a specific p38 MAPK–ATF-7 pathway orchestrates cross-tissue potassium homeostasis in Caenorhabditis elegans. It drives transcriptional upregulation of a crucial P-type ATPase pump CATP-3 specifically in the hypodermis, a process integrates cell-autonomous mechanisms with non-autonomous ASI neuronal signals, thereby enhancing organismal survival during potassium deficiency. Notably, this regulation is distinct from canonical osmotic stress responses, revealing a specialized and conserved survival strategy. Analogous p38-mediated control of P-type ATPases occurs in yeast and mammalian cells, suggesting broad relevance. Our findings redefine potassium regulation as a cross-tissue process linked to lifespan, stress signaling, and innate immunity with potential implications for aging and age-related diseases. Biological sciences/Physiology/Ageing Biological sciences/Cell biology/Cell signalling/Stress signalling Biological sciences/Cell biology/Mechanisms of disease low potassium C. elegans P-type ATPases p38 MAPK Tissue-specific lifespan innate immunity aging non-autonomous Full Text Additional Declarations There is NO Competing Interest. Supplementary Files DataS1.xlsx Supplementary Data 1 MovieS1sek1100mMNaCl2h.mp4 Supplementary Video 1 MovieS2sek1100mMKCl2h.mp4 Supplementary Video 2 MovieS3sek1100mMNaCl24h.mp4 Supplementary Video 3 MovieS4sek1100mMKCl24h.mp4 Supplementary Video 4 MovieS5catp3100mMNaCl48h.mp4 Supplementary Video 5 MovieS6catp3100mMKCl48h.mp4 Supplementary Video 6 Cite Share Download PDF Status: Published Journal Publication published 09 Mar, 2026 Read the published version in Nature Communications → Version 1 posted You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. We do this by developing innovative software and high quality services for the global research community. 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Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-7350614","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Article","associatedPublications":[],"authors":[{"id":513402160,"identity":"47c119b9-a5a2-496d-b266-95106a43b05f","order_by":0,"name":"Ziyun 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