{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,22]],"date-time":"2026-07-22T20:48:30Z","timestamp":1784753310894,"version":"3.55.0"},"reference-count":44,"publisher":"MDPI AG","issue":"11","license":[{"start":{"date-parts":[[2024,6,4]],"date-time":"2024-06-04T00:00:00Z","timestamp":1717459200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001691","name":"JSPS KAKENHI","doi-asserted-by":"publisher","award":["18H02971"],"award-info":[{"award-number":["18H02971"]}],"id":[{"id":"10.13039\/501100001691","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001691","name":"JSPS KAKENHI","doi-asserted-by":"publisher","award":["17K08275"],"award-info":[{"award-number":["17K08275"]}],"id":[{"id":"10.13039\/501100001691","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Metabolic dysfunction-associated fatty liver disease (MAFLD) is one of the most common chronic liver diseases worldwide. Some patients with MAFLD develop metabolic dysfunction-associated steatohepatitis (MASH), which can lead to severe liver fibrosis. However, the molecular mechanisms underlying this progression remain unknown, and no effective treatment for MASH has been developed so far. In this study, we performed a longitudinal detailed analysis of mitochondria in the livers of choline-deficient, methionine-defined, high-fat-diet (CDAHFD)-fed mice, which exhibited a MASH-like pathology. We found that FoF1\u2013ATPase activity began to decrease in the mitochondria of CDAHFD-fed mice prior to alterations in the activity of mitochondrial respiratory chain complex, almost at the time of onset of liver fibrosis. In addition, the decrease in FoF1\u2013ATPase activity coincided with the accelerated opening of the mitochondrial permeability transition pore (PTP), for which FoF1\u2013ATPase might be a major component or regulator. As fibrosis progressed, mitochondrial permeability transition (PT) induced in CDAHFD-fed mice became less sensitive to cyclosporine A, a specific PT inhibitor. These results suggest that episodes of fibrosis might be related to the disruption of mitochondrial function via PTP opening, which is triggered by functional changes in FoF1\u2013ATPase. These novel findings could help elucidate the pathogenesis of MASH and lead to the development of new therapeutic strategies.<\/jats:p>","DOI":"10.3390\/ijms25116193","type":"journal-article","created":{"date-parts":[[2024,6,4]],"date-time":"2024-06-04T11:48:50Z","timestamp":1717501730000},"page":"6193","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Longitudinal Analysis of Mitochondrial Function in a Choline-Deficient L-Amino Acid-Defined High-Fat Diet-Induced Metabolic Dysfunction-Associated Steatohepatitis Mouse Model"],"prefix":"10.3390","volume":"25","author":[{"given":"Akiko","family":"Yamada","sequence":"first","affiliation":[{"name":"Department of Pathology, Nihon University School of Dentistry, Chiyoda-ku, Tokyo 101-8310, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Akira","family":"Watanabe","sequence":"additional","affiliation":[{"name":"Institute for Genome Research, Tokushima University, Kuramoto, Tokushima 770-8503, Japan"},{"name":"Faculty of Pharmaceutical Sciences, Tokushima University, Shomachi, Tokushima 770-8505, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Atsushi","family":"Nara","sequence":"additional","affiliation":[{"name":"Institute for Genome Research, Tokushima University, Kuramoto, Tokushima 770-8503, Japan"},{"name":"Faculty of Pharmaceutical Sciences, Tokushima University, Shomachi, Tokushima 770-8505, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1087-8338","authenticated-orcid":false,"given":"Naozumi","family":"Ishimaru","sequence":"additional","affiliation":[{"name":"Department of Oral Pathology, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University, Bunkyo-ku, Tokyo 113-8549, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kosuke","family":"Maeda","sequence":"additional","affiliation":[{"name":"Institute for Genome Research, Tokushima University, Kuramoto, Tokushima 770-8503, Japan"},{"name":"Faculty of Pharmaceutical Sciences, Tokushima University, Shomachi, Tokushima 770-8505, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yusuke","family":"Ido","sequence":"additional","affiliation":[{"name":"Institute for Genome Research, Tokushima University, Kuramoto, Tokushima 770-8503, Japan"},{"name":"Faculty of Pharmaceutical Sciences, Tokushima University, Shomachi, Tokushima 770-8505, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9869-1177","authenticated-orcid":false,"given":"Kazumasa","family":"Kotake","sequence":"additional","affiliation":[{"name":"Institute for Genome Research, Tokushima University, Kuramoto, Tokushima 770-8503, Japan"},{"name":"Faculty of Pharmaceutical Sciences, Tokushima University, Shomachi, Tokushima 770-8505, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Masatake","family":"Asano","sequence":"additional","affiliation":[{"name":"Department of Pathology, Nihon University School of Dentistry, Chiyoda-ku, Tokyo 101-8310, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5331-3508","authenticated-orcid":false,"given":"Yasuo","family":"Shinohara","sequence":"additional","affiliation":[{"name":"Institute for Genome Research, Tokushima University, Kuramoto, Tokushima 770-8503, Japan"},{"name":"Faculty of Pharmaceutical Sciences, Tokushima University, Shomachi, Tokushima 770-8505, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Takenori","family":"Yamamoto","sequence":"additional","affiliation":[{"name":"Institute for Genome Research, Tokushima University, Kuramoto, Tokushima 770-8503, Japan"},{"name":"Faculty of Pharmaceutical Sciences, Tokushima University, Shomachi, Tokushima 770-8505, Japan"},{"name":"Division of Molecular Target and Gene Therapy Products, National Institute of Health Sciences, Kawasaki-ku, Kanagawa 210-9501, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2024,6,4]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1335","DOI":"10.1097\/HEP.0000000000000004","article-title":"The global epidemiology of nonalcoholic fatty liver disease (NAFLD) and nonalcoholic steatohepatitis (NASH): A systematic review","volume":"77","author":"Younossi","year":"2023","journal-title":"Hepatology"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"2183","DOI":"10.1185\/03007995.2010.506375","article-title":"Population-based risk factors and resource utilization for HCC: US perspective","volume":"26","author":"Sanyal","year":"2010","journal-title":"Curr. 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