TACO1 regulates mitochondrial adaptation in hypertension-induced cardiac remodeling and heart failure

TACO1 regulates mitochondrial adaptation in hypertension-induced cardiac remodeling and heart failure | 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 TACO1 regulates mitochondrial adaptation in hypertension-induced cardiac remodeling and heart failure Berwin Singh Swami Vetha, Ronald McMillan, James Marchant, Mohd Mabood Khan, and 19 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-9589283/v1 This work is licensed under a CC BY 4.0 License Status: Posted Version 1 posted You are reading this latest preprint version Abstract Mitochondrial dysfunction drives hypertensive heart failure and reflects impaired oxidative phosphorylation and altered organelle structure. The mechanisms linking hypertensive signaling to mitochondrial translation and architecture remain unclear. TACO1 is a mitochondrial translational activator required for cytochrome c oxidase subunit I synthesis and may regulate respiratory chain assembly. We tested whether angiotensin II type 1 receptor activation disrupts TACO1-dependent translation and drives inner membrane remodeling. Using mRen also known as (mRen2)27 hypertensive rat hearts, we assessed mitochondrial function, ultrastructure, and metabolism. AT1R activation reduced TACO1-dependent COX I translation and produced a selective deficiency in complex IV activity. This impaired oxidative phosphorylation and increased the production of reactive oxygen species. Mitochondria exhibited reduced volume, increased fragmentation, and disrupted cristae organization with lower integrity scores. Hypertensive hearts also showed reduced expression of OPA1 and MICOS components. Metabolomic profiling separated control and heart failure groups and revealed enrichment of amino acid, nucleotide, and mitochondrial energy pathways. Lipidomic analysis identified coordinated changes across lipid classes consistent with altered membrane composition. Pharmacological AT1R inhibition restored COX I translation, rescued complex IV activity, and improved cristae structure. These findings establish a mechanistic link between hypertensive signaling, mitochondrial translation, cristae organization, and metabolic remodeling in heart failure. General Cell Biology & Physiology Cellular Metabolism Clinical Pharmacology Cardiac & Cardiovascular Systems TACO1 Complex IV Hypertensive heart failure Renin–angiotensin system (mRen2)27 transgenic rat Metabolic remodeling Full Text Additional Declarations The authors declare no competing interests. Supplementary Files 2TACO1Supplement.docx TACO1 Supplement Cite Share Download PDF Status: Posted 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-9589283","acceptedTermsAndConditions":true,"allowDirectSubmit":true,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":633131443,"identity":"955a6c16-2c40-4da8-9d86-311a0a54bbfb","order_by":0,"name":"Berwin Singh Swami Vetha","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAA8klEQVRIiWNgGAWjYLCCBCA2YOBhfJBQARGQIEaLBFALs8GHM8RqYYBoYZOc2UaEFvkZyU83PGyzqTNnP3tAmneejbzBAeaDt3nwaDG4kWZ2I7EtTcKyJy/BmHdbmuGGA2zJ1ni1SCeY3Ug4c1jC4ECOQTLvtsMJBgd4zKTxaZGfnf4NqOW/hMH5NwaHeef8B2rh/4ZXC8PtHKAtFQckDG7kGDbObDgAsoUNrxaD+2/KgFqSJTfceJfM8OFYsuHMw2zGlnPwOazn+LabPwzs+A3O5x7/kVBjJ893vPnhjTf4HIYJmElTPgpGwSgYBaMACwAAdb5R/oB3gv4AAAAASUVORK5CYII=","orcid":"https://orcid.org/0000-0002-0264-4219","institution":"Department of Foundational Science, East Carolina University, Greenville, NC, USA","correspondingAuthor":true,"prefix":"","firstName":"Berwin","middleName":"Singh Swami","lastName":"Vetha","suffix":""},{"id":633151901,"identity":"26bac416-e010-4438-a0ae-1293f051a88b","order_by":1,"name":"Ronald McMillan","email":"","orcid":"https://orcid.org/0000-0002-8363-8805","institution":"Department of Pharmacology and Toxicology, East Carolina University, Greenville, NC, USA","correspondingAuthor":false,"prefix":"","firstName":"Ronald","middleName":"","lastName":"McMillan","suffix":""},{"id":633151902,"identity":"aa82efff-bd0b-404c-8855-3ec6dad81013","order_by":2,"name":"James Marchant","email":"","orcid":"https://orcid.org/0000-0002-9551-835X","institution":"Development, Aging and Regeneration Program, Sanford Burnham Prebys Medical Discovery Institute, La Jolla, CA, USA","correspondingAuthor":false,"prefix":"","firstName":"James","middleName":"","lastName":"Marchant","suffix":""},{"id":633151903,"identity":"611ea8a0-d49a-4f3d-963e-817aaf94764d","order_by":3,"name":"Mohd Mabood Khan","email":"","orcid":"","institution":"Department of Medicine, Division of Genetic Medicine \u0026 Clinical Pharmacology, Vanderbilt University Medical Center, Nashville, TN, USA","correspondingAuthor":false,"prefix":"","firstName":"Mohd","middleName":"Mabood","lastName":"Khan","suffix":""},{"id":633151904,"identity":"7c55f813-76c9-4554-86ef-6633fbc1287e","order_by":4,"name":"Joyonna Gamble George","email":"","orcid":"https://orcid.org/0000-0002-5492-9216","institution":"Department of Computer Science, Whiting School of Engineering, Johns Hopkins University, Baltimore, MD 21218, USA","correspondingAuthor":false,"prefix":"","firstName":"Joyonna","middleName":"Gamble","lastName":"George","suffix":""},{"id":633151905,"identity":"a7c12885-0056-4d36-a3a8-f7d67bc19e63","order_by":5,"name":"Jeremiah Afolabi","email":"","orcid":"","institution":"Department of Molecular Physiology and Biophysics, Vanderbilt University, Nashville, TN, USA","correspondingAuthor":false,"prefix":"","firstName":"Jeremiah","middleName":"","lastName":"Afolabi","suffix":""},{"id":633151906,"identity":"f0a3769d-954d-4a2b-9c7f-ac6a9fcdcf65","order_by":6,"name":"Edgar Garza Lopez","email":"","orcid":"","institution":"Department of Internal Medicine, University of Iowa, Iowa City, IA, USA","correspondingAuthor":false,"prefix":"","firstName":"Edgar","middleName":"Garza","lastName":"Lopez","suffix":""},{"id":633151907,"identity":"b7871d86-0dbe-4778-88a4-6dcfacc5cdcc","order_by":7,"name":"Andrea G. 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