Organelles harbour pH gradients

Organelles harbour pH gradients | 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 Organelles harbour pH gradients Yamuna Krishnan, Sangyoon Lee, Sandip Chakraborty, Soyoung Kim, and 5 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-8395568/v1 This work is licensed under a CC BY 4.0 License Status: Under Review Version 1 posted You are reading this latest preprint version Abstract Organelle pH is critical to organelle identity and function. Resident proteins that define each organelle modify transiting cargo proteins, with both retention and trafficking between organelles governed by pH-dependent mechanisms. For example, lysosomal enzymes bind mannose-6-phosphate receptors at the higher pH (~6.5) of the Golgi and dissociate at the lower pH (~5.5) of late endosomes. Proteins that stray from the endoplasmic reticulum (ER) are captured by KDEL receptors in the acidic Golgi and returned into the neutral ER. This pH-tuned trafficking system compartmentalizes organelle function and prevents mis-localization of critical enzymes. Dysregulated organelle pH disrupts their function and leads to various diseases. Because protons move rapidly in water, the pH within a single organelle is currently assumed to be spatially uniform. Here, using a reporter sensitive from pH 5.5 - 10.5 to map a spectrum of organelles at high resolution, we discovered that pH gradients exist within single, large or long organelles such as the ER and mitochondria, and in membrane-less organelles without ion-transporting proteins such as the nucleolus. These new findings upend our understanding of organellar pH, prompting new questions about proton diffusion within the cell, and its potential consequences on organelle function. Biological sciences/Chemical biology/Biophysical chemistry Physical sciences/Chemistry/Analytical chemistry/Imaging studies Physical sciences/Chemistry/Analytical chemistry/Fluorescent probes Biological sciences/Cell biology/Organelles/Mitochondria Biological sciences/Cell biology/Organelles Full Text Additional Declarations There is NO Competing Interest. Supplementary Files SeRapHinExtendedDataFiguresver4.pdf Extended Data Figures MitoMatrixRbyG2.avi Supplementary Video 3 MitoMatrixRbyG3.avi Supplementary Video 2 MitoMatrixRbyG1.avi Supplementary Video 1 SISeRapHinver5.pdf Supplementary information file Cite Share Download PDF Status: Under Review 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. Our growing team is made up of researchers and industry professionals working together to solve the most critical problems facing scientific publishing. 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-8395568","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Article","associatedPublications":[],"authors":[{"id":576480830,"identity":"792c01bc-93d9-4639-8d8f-1a5d0a6eebd5","order_by":0,"name":"Yamuna 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