{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,10]],"date-time":"2026-10-10T20:56:52Z","timestamp":1791665812477,"version":"4.3.4"},"reference-count":69,"publisher":"Wiley","issue":"11","license":[{"start":{"date-parts":[[2023,8,24]],"date-time":"2023-08-24T00:00:00Z","timestamp":1692835200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Liver International"],"published-print":{"date-parts":[[2023,11]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>This thematic review aims to provide an overview of the current state of knowledge about the occurrence of giant mitochondria or megamitochondria in liver parenchymal cells. Their presence and accumulation are considered to be a major pathological hallmark of the health and fate of liver parenchymal cells that leads to overall tissue deterioration and eventually results in organ failure. The first description on giant mitochondria dates back to the 1960s, coinciding with the availability of the first generation of electron microscopes in clinical diagnostic laboratories. Detailed accounts on their ultrastructure have mostly been described in patients suffering from alcoholic liver disease, chronic hepatitis, hepatocellular carcinoma and non\u2010alcoholic fatty liver disease. Interestingly, from this extensive literature survey, it became apparent that giant mitochondria or megamitochondria present themselves with or without highly organised crystal\u2010like intramitochondrial inclusions. The origin, formation and potential role of giant mitochondria remain to\u2010date largely unanswered. Likewise, the biochemical composition of the well\u2010organised crystal\u2010like inclusions and their possible impact on mitochondrial function is unclear. Herein, concepts about the possible mechanism of their formation and three\u2010dimensional architecture will be approached. We will furthermore discuss their importance in diagnostics, including future research outlooks and potential therapeutic interventions to cure liver disease where giant mitochondria are implemented.<\/jats:p>","DOI":"10.1111\/liv.15711","type":"journal-article","created":{"date-parts":[[2023,8,24]],"date-time":"2023-08-24T10:33:20Z","timestamp":1692873200000},"page":"2365-2378","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":20,"title":["Giant mitochondria in human liver disease"],"prefix":"10.1111","volume":"43","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-2094-1740","authenticated-orcid":false,"given":"Gerald J.","family":"Shami","sequence":"first","affiliation":[{"name":"School of Medical Sciences (Molecular and Cellular Biomedicine) The University of Sydney  Sydney New South Wales Australia"},{"name":"Australian Centre for Microscopy and Microanalysis The University of Sydney  Sydney New South Wales Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Iryna V.","family":"Samarska","sequence":"additional","affiliation":[{"name":"Pathology Maastricht University Medical Center  Maastricht The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ger H.","family":"Koek","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine division of Gastroenterology &amp; Hepatology Maastricht University Medical Center  Maastricht The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5413-3771","authenticated-orcid":false,"given":"Amy","family":"Li","sequence":"additional","affiliation":[{"name":"Centre for Healthy Futures Torrens University Australia  Sydney New South Wales Australia"},{"name":"Department of Pharmacy &amp; Biomedical Sciences La Trobe University  Melbourne Victoria Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elena","family":"Palma","sequence":"additional","affiliation":[{"name":"The Roger Williams Institute of Hepatology, Foundation for Liver Research  London UK"},{"name":"King's College London, Faculty of Life Sciences and Medicine  London UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shilpa","family":"Chokshi","sequence":"additional","affiliation":[{"name":"King's College London, Faculty of Life Sciences and Medicine  London UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eddie","family":"Wisse","sequence":"additional","affiliation":[{"name":"Division of Nanoscopy Multimodal Molecular Imaging Institute, University of Maastricht  Maastricht The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5222-0895","authenticated-orcid":false,"given":"Filip","family":"Braet","sequence":"additional","affiliation":[{"name":"School of Medical Sciences (Molecular and Cellular Biomedicine) The University of Sydney  Sydney New South Wales Australia"},{"name":"Australian Centre for Microscopy and Microanalysis The University of Sydney  Sydney New South Wales Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2023,8,24]]},"reference":[{"key":"e_1_2_14_2_1","doi-asserted-by":"publisher","DOI":"10.1084\/jem.81.1.51"},{"key":"e_1_2_14_3_1","doi-asserted-by":"publisher","DOI":"10.1177\/1.4.188"},{"key":"e_1_2_14_4_1","first-page":"111","volume-title":"Entering an unseen world","author":"Moberg CL","year":"2012"},{"issue":"2","key":"e_1_2_14_5_1","first-page":"619","article-title":"Cytochemical studies of mammalian tissues; isolation of intact mitochondria from rat liver; some biochemical properties of mitochondria and submicroscopic particulate material","volume":"172","author":"Hogeboom GH","year":"1948","journal-title":"J Biochem"},{"key":"e_1_2_14_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0022-5320(66)80027-8"},{"key":"e_1_2_14_7_1","first-page":"54","volume-title":"Ultrastructure of the Mammalian Cell: An Atlas","author":"Krsti\u0107 RV","year":"1979"},{"key":"e_1_2_14_8_1","first-page":"135","article-title":"Parakristalline Einschu\u00dfk\u00f6rper der mitochondrien des menschlichen leberparenchyms. 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