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Lysosomes are early storage sites, but mitochondria are highly vulnerable to copper toxicity. A systematic review and meta-analysis evaluated mitochondrial outcomes in Wilson disease patients and animal models, integrating hepatic copper, morphology, oxidative stress, mtDNA copy number, ATP production, and respiratory complex activities.",{"@graph":69,"@context":122},[70,84,105],{"@type":71,"itemListElement":72},"BreadcrumbList",[73,77,79,82],{"item":74,"name":75,"@type":76,"position":8},"https://docshare.wps.com","Home","ListItem",{"item":78,"name":9,"@type":76,"position":14},"https://docshare.wps.com/document/",{"item":80,"name":35,"@type":76,"position":81},"https://docshare.wps.com/document/healthcare/",3,{"item":83,"name":65,"@type":76,"position":19},"https://docshare.wps.com/document/mitochondrial-dysfunction-in-wilson-disease-a-systematic-review-and-metaanalysis-across-human-and-animal-models/407400/",{"url":83,"name":65,"@type":85,"image":86,"author":91,"headline":65,"publisher":94,"fileFormat":97,"inLanguage":63,"description":67,"dateModified":98,"datePublished":99,"encodingFormat":97,"isAccessibleForFree":100,"interactionStatistic":101},"DigitalDocument",{"url":87,"@type":88,"width":89,"height":90},"https://docshare.wps.com/thumbnails/mitochondrial-dysfunction-in-wilson-disease-a-systematic-review-and-metaanalysis-across-human-and-animal-models/407400.png","ImageObject",300,407,{"name":92,"@type":93},"Aurelia","Person",{"url":74,"name":95,"@type":96},"DocShare","Organization","application/pdf","2026-11-03","2026-09-28",true,{"@type":102,"interactionType":103,"userInteractionCount":44},"InteractionCounter",{"@type":104},"ViewAction",{"@type":106,"mainEntity":107},"FAQPage",[108,114,118],{"name":109,"@type":110,"acceptedAnswer":111},"What outcomes were assessed in the systematic review and meta-analysis?","Question",{"text":112,"@type":113},"The review assessed hepatic mitochondrial copper, morphology, oxidative stress, mtDNA copy number, ATP production, and respiratory complex activities across Wilson disease patients and animal models.","Answer",{"name":115,"@type":110,"acceptedAnswer":116},"What were the main mitochondrial findings in Wilson disease?",{"text":117,"@type":113},"Mitochondrial copper was consistently elevated, ultrastructural abnormalities increased, oxidative stress markers rose, mtDNA copy number decreased, and ATP synthesis and respiratory complex activities were impaired.",{"name":119,"@type":110,"acceptedAnswer":120},"How does the review interpret the timing and progression of mitochondrial dysfunction?",{"text":121,"@type":113},"Mitochondrial dysfunction was described as arising early and worsening with disease progression, with several abnormalities observed in presymptomatic or young animals.","https://schema.org",{"og:url":83,"og:type":124,"og:title":65,"og:site_name":95,"og:description":67},"article",{"robots":126,"canonical":83},"index,follow",{"doc_id":128,"site_id":62},407400,1790815788,{"code":4,"msg":5,"data":131},{"doc_id":128,"user_id":132,"nickname":92,"user_avatar":133,"doc_module":4,"category_id":34,"category_name":35,"doc_title":65,"doc_description":67,"doc_content":134,"file_id":135,"file_url":136,"file_type":137,"file_size":138,"view_count":44,"is_deleted":4,"is_public":8,"is_downloadable":8,"audit_status":8,"page_count":139,"language":140,"language_code":63,"site_id":62,"html_lang":63,"table_of_contents":141,"faqs":142,"seo_title":143,"seo_description":67,"update_tm":144,"read_time":145,"preview_page_count":4},1099514068365,"https://ap-avatar.wpscdn.com/avatar/10000253d8d9f28188e?_k=1776742907772140068","TYPE Systematic Review PUBLISHED 17 December 2025 DOI 10.3389/fmolb.2025.1712573  \nOPEN ACCESS  \nEDITED BY  \nRicardo Lagoa,  \nPolytechnic Institute of Leiria, Portugal  \nREVIEWED BY  \nFareed Khdair Ahmad, The University of Jordan School of Medicine, Jordan  \nPeili Huang,  \nCapital Medical University, China  \n*CORRESPONDENCE  \nCecilia Giulivi,  \n [cgiulivi@ucdavis.edu](cgiulivi@ucdavis.edu)  \nRECEIVED 24 September 2025  \nREVISED 21 November 2025  \nACCEPTED 24 November 2025  \nPUBLISHED 17 December 2025  \nCITATION  \nAmin R, Medici V, Fausak ED, Sierra K, Li I, Gong J and Giulivi C (2025) Mitochondrial dysfunction in Wilson disease: a systematic review and meta–analysis across human and animal models.  \nFront. Mol. Biosci. 12:1712573 .  \ndoi: 10.3389/fmolb.2025.1712573  \nCOPYRIGHT  \n© 2025 Amin, Medici, Fausak, Sierra, Li, Gong and Giulivi. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY) . The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.  \nMitochondrial dysfunction in Wilson disease: a systematic review and meta–analysis across human and animal models  \nRaya Amin 1, Valentina Medici 2, Erik D. Fausak 3, Keren Sierra 1, Ieleen Li 1, Joshua Gong 1 and Cecilia Giulivi 1,4*  \n1 Department of Molecular Biosciences, School of Veterinary Medicine, University of California, Davis, CA, United States, 2 Department of Internal Medicine, Division of Gastroenterology and Hepatology, University of California, Davis, CA, United States, 3 University Library, University of California, Davis, CA, United States, 4 Medical Investigations of Neurodevelopmental Disorders (M. I. N. D.) Institute, University of California, Davis, CA, United States  \nBackground & Aims: Wilson disease (WD) is a genetic disorder of copper metabolism caused by ATP7B mutations, leading to hepatic and systemic copper accumulation. While lysosomes are early storage sites, mitochondria appear highly vulnerable to copper toxicity. We performed a systematic review and meta–analysis to assess mitochondrial outcomes in WD patients and animal models.  \nMethods: PubMed, Scopus, and SciFinder were searched through 11 September 2025, for studies reporting hepatic mitochondrial endpoints in WD (in patients and models using mice, rats, and dogs) . Outcomes included mitochondrial copper, morphology, oxidative stress, mtDNA copy number, ATP production, and respiratory Complex activities. Random–effects meta–analyses were conducted.  \nResults: Thirteen studies met the inclusion criteria. Mitochondrial copper was consistently elevated (standardized mean difference ±standard error: 6.7 ± 0.9, P \u003C 0.001), with ultrastructural abnormalities (4 ± 2, P = 0.012) . Oxidative stress markers increased (2 .9 ± 0.9, P = 0.001), while MnSOD and aconitase declined with disease progression. mtDNA copy number was reduced (−0 .7 ± 0.3, P = 0.032) . ATP synthesis (−1 .5 ± 0.6, P = 0.023) and Complex activities (−1 .0 ± 0.3, P = 0.001) were impaired, especially in older or symptomatic subjects. Citrate synthase activity increased (2 .8 ± 0.9, P = 0.003), consistent with compensatory biogenesis. Several abnormalities appeared in presymptomatic or young animals.  \nConclusion: Across human and animal studies, hepatic mitochondria in WD exhibit copper accumulation, structural injury, impaired bioenergetics, oxidative stress, and mitochondrial genome loss. Mitochondrial dysfunction arises early and worsens with progression, highlighting it as a central pathogenic feature and therapeutic target.  \nKEYWORDS  \ncopper toxicity, complex IV, citrate synthase, oxidative stress, MtDNA copy number, bioenergetics, liver metabolism, translational hepatology  \nFrontiers in Molecular","cbCait3NKt3gx2Za","https://ap.wps.com/l/cbCait3NKt3gx2Za","pdf",3159439,17,"English","# Background & Aims\n# Methods\n# Results\n# Conclusion\n# Highlights\n# Introduction","[{\"question\":\"What outcomes were assessed in the systematic review and meta-analysis?\",\"answer\":\"The review assessed hepatic mitochondrial copper, morphology, oxidative stress, mtDNA copy number, ATP production, and respiratory complex activities across Wilson disease patients and animal models.\"},{\"question\":\"What were the main mitochondrial findings in Wilson disease?\",\"answer\":\"Mitochondrial copper was consistently elevated, ultrastructural abnormalities increased, oxidative stress markers rose, mtDNA copy number decreased, and ATP synthesis and respiratory complex activities were impaired.\"},{\"question\":\"How does the review interpret the timing and progression of mitochondrial dysfunction?\",\"answer\":\"Mitochondrial dysfunction was described as arising early and worsening with disease progression, with several abnormalities observed in presymptomatic or young animals.\"}]","Mitochondrial dysfunction in Wilson disease - a systematic review and meta–analysis across human and animal models | PDF",1790573640,43]