{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,21]],"date-time":"2026-09-21T15:40:19Z","timestamp":1790005219806,"version":"4.0.1"},"reference-count":47,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2012,12,11]],"date-time":"2012-12-11T00:00:00Z","timestamp":1355184000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"name":"Ministry of Education, Culture, Sports and Science and Technology","award":["21590366"],"award-info":[{"award-number":["21590366"]}]},{"name":"Ministry of Education, Culture, Sports and Science and Technology","award":["24590409"],"award-info":[{"award-number":["24590409"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Liver International"],"published-print":{"date-parts":[[2013,2]]},"abstract":"Abstract<\/jats:title>\n \n Background\/Aims<\/jats:title>\n \n We have reported the involvement of deregulated autophagy and subsequent cellular senescence in biliary epithelial lesions in primary biliary cirrhosis (\n PBC<\/jats:styled-content>\n ). Given that mitochondria are a major target of autophagy, we hypothesized that deregulated autophagy of mitochondria may be involved in autoimmune pathogenesis in\n PBC<\/jats:styled-content>\n .\n <\/jats:p>\n <\/jats:sec>\n \n Methods<\/jats:title>\n \n We examined immunohistochemically the expression of pyruvate dehydrogenase complex\u2010E2 component (\n PDC<\/jats:styled-content>\n \u2010E2) and cytochrome c oxidase, subunit I (\n CCO<\/jats:styled-content>\n ), in livers taken from patients with\n PBC<\/jats:styled-content>\n (\n n<\/jats:italic>\n \u00a0=\u00a042) and control livers (\n n<\/jats:italic>\n \u00a0=\u00a076). The colocalization of mitochondrial antigens with an autophagy marker microtubule\u2010associated protein\u2010light chain 3\u03b2 (\n LC<\/jats:styled-content>\n 3), a deregulated autophagy marker p62\/sequestosome\u20101 (p62) and a lysosomal marker\n LAMP<\/jats:styled-content>\n \u20101 was examined by double immunofluorescence. We examined the colocalization of mitochondrial antigens with\n LC<\/jats:styled-content>\n 3, p62 and\n LAMP<\/jats:styled-content>\n \u20101 and the cell\u2010surface expression of\n PDC<\/jats:styled-content>\n \u2010E2 in cultured biliary epithelial cells (\n BEC<\/jats:styled-content>\n s) treated with various stresses.\n <\/jats:p>\n <\/jats:sec>\n \n Results<\/jats:title>\n \n Intense granular expression of\n PDC<\/jats:styled-content>\n \u2010E2 and\n CCO<\/jats:styled-content>\n was seen in the damaged small bile ducts (\n SBD<\/jats:styled-content>\n s) in\n PBC<\/jats:styled-content>\n and the expression was significantly more frequent in\n PBC<\/jats:styled-content>\n than in control livers (\n P<\/jats:italic>\n \u00a0<\u00a00.01). The granular expression of mitochondrial antigens was colocalized with\n LC<\/jats:styled-content>\n 3 in damaged\n SBD<\/jats:styled-content>\n s in\n PBC<\/jats:styled-content>\n . The accumulation of\n LC<\/jats:styled-content>\n 3\u2010expressing punctae colocalized with\n PDC<\/jats:styled-content>\n \u2010E2 and\n CCO<\/jats:styled-content>\n was significantly more increased in cultured\n BEC<\/jats:styled-content>\n s treated with various stresses. The cell\u2010surface expression of\n PDC<\/jats:styled-content>\n \u2010E2 was induced by various stresses in\n BEC<\/jats:styled-content>\n s.\n <\/jats:p>\n <\/jats:sec>\n \n Conclusion<\/jats:title>\n \n Deregulated autophagy may contribute to the abnormal expression of mitochondrial antigens and may be involved in the autoimmune pathogenesis of bile duct lesions in\n PBC<\/jats:styled-content>\n .\n <\/jats:p>\n <\/jats:sec>","DOI":"10.1111\/liv.12049","type":"journal-article","created":{"date-parts":[[2012,11,12]],"date-time":"2012-11-12T07:00:20Z","timestamp":1352703620000},"page":"312-320","source":"Crossref","is-referenced-by-count":66,"title":["Increased expression of mitochondrial proteins associated with autophagy in biliary epithelial lesions in primary biliary cirrhosis"],"prefix":"10.1111","volume":"33","author":[{"given":"Motoko","family":"Sasaki","sequence":"first","affiliation":[{"name":"Department of Human Pathology Kanazawa University Graduate School of Medicine 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