Taurine can restrict mtdsRNA mediated pyroptosis by enhancing mitophagy in nucleus pulposus cells

Taurine can restrict mtdsRNA mediated pyroptosis by enhancing mitophagy in nucleus pulposus cells | 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 Research Article Taurine can restrict mtdsRNA mediated pyroptosis by enhancing mitophagy in nucleus pulposus cells Zixuan Ou, Junyu Wei, Bide Tong, Jie Lei, Huaizhen Liang, Dingchao Zhu, and 12 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-5630037/v1 This work is licensed under a CC BY 4.0 License Status: Published Journal Publication published 09 Oct, 2025 Read the published version in Cell Communication and Signaling → Version 1 posted 7 You are reading this latest preprint version Abstract Mitochondrial double-stranded RNA (mtdsRNA), a long-stranded RNA molecule generated by bidirectional transcription of the circular mitochondrial genome, can trigger the type 1 interferon response by activating pattern recognition receptors in the cytoplasm during mitochondrial dysfunction. However, its regulatory and pathogenic mechanisms in intervertebral disc degeneration are poorly understood. Here, we showed that mtdsRNA was abnormally elevated in degenerative nucleus pulposus tissues. Furthermore, we found that mtdsRNA leakage into the cytoplasm could cause MAVS oligomerization by binding to RLRs, and oligomerized MAVS could then promote nucleus pulposus cell pyroptosis by activating NLRP3. To further elucidate the upstream regulatory mechanism of mtdsRNA, we performed untargeted metabolomics analysis, which revealed that the downregulation of taurine under external stimuli could drive an imbalance in mtdsRNA homeostasis. RNA-seq further revealed that exogenous supplementation with taurine protected cells from mtdsRNA-induced pyroptosis by increasing mitophagy. In conclusion, our study links taurine metabolism, mitochondrial nucleic acids and pyroptosis and suggests that mtdsRNA is an important causative molecule and a potential therapeutic target in intervertebral disc degeneration. mtdsRNA pyroptosis taurine mitophagy intervertebral disc degeneration Full Text Additional Declarations No competing interests reported. Supplementary Files Supplementarymaterials.docx sourcedata.docx Cite Share Download PDF Status: Published Journal Publication published 09 Oct, 2025 Read the published version in Cell Communication and Signaling → Version 1 posted Editorial decision: Accepted 06 Sep, 2025 Reviewers agreed at journal 18 Aug, 2025 Reviews received at journal 05 May, 2025 Reviewers agreed at journal 13 Apr, 2025 Reviewers invited by journal 13 Apr, 2025 Submission checks completed at journal 11 Apr, 2025 First submitted to journal 11 Apr, 2025 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-5630037","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":442265334,"identity":"a7a77679-100f-448c-9d65-6253aefeeafb","order_by":0,"name":"Zixuan Ou","email":"","orcid":"","institution":"Huazhong University of Science and Technology","correspondingAuthor":false,"prefix":"","firstName":"Zixuan","middleName":"","lastName":"Ou","suffix":""},{"id":442265335,"identity":"fc0a1f54-5db3-4181-91f6-77af3d7c29a3","order_by":1,"name":"Junyu Wei","email":"","orcid":"","institution":"Huazhong University of Science and 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