{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,19]],"date-time":"2026-09-19T08:17:39Z","timestamp":1789805859948,"version":"4.0.1"},"reference-count":48,"publisher":"Wiley","issue":"12","license":[{"start":{"date-parts":[[2013,11,12]],"date-time":"2013-11-12T00:00:00Z","timestamp":1384214400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Genes to Cells"],"published-print":{"date-parts":[[2013,12]]},"abstract":"<jats:p><jats:styled-content style=\"fixed-case\">VCP<\/jats:styled-content>\/p97 is a hexameric ring\u2010shaped <jats:styled-content style=\"fixed-case\">AAA<\/jats:styled-content><jats:sup>+<\/jats:sup> <jats:styled-content style=\"fixed-case\">ATP<\/jats:styled-content>ase that participates in various ubiquitin\u2010associated cellular functions. Mis\u2010sense mutations in <jats:italic><jats:styled-content style=\"fixed-case\">VCP<\/jats:styled-content><\/jats:italic> gene are associated with the pathogenesis of two inherited diseases: inclusion body myopathy associated with Paget's disease of the bone and front\u2010temporal dementia (<jats:styled-content style=\"fixed-case\">IBMPFD<\/jats:styled-content>) and familial amyotrophic lateral sclerosis (<jats:styled-content style=\"fixed-case\">ALS<\/jats:styled-content>). These pathogenic <jats:styled-content style=\"fixed-case\">VCP<\/jats:styled-content>s have higher affinities for several cofactors, including Npl4, Ufd1 and p47. In Parkin\u2010dependent mitochondrial quality control systems, <jats:styled-content style=\"fixed-case\">VCP<\/jats:styled-content> migrates to damaged mitochondria (e.g., those treated with uncouplers) to aid in the degradation of mitochondrial outer membrane proteins and to eliminate mitochondria. We showed that endogenous Npl4 and p47 also migrate to mitochondria after uncoupler treatment, and <jats:italic>Npl4, Ufd1<\/jats:italic> or <jats:italic>p47<\/jats:italic> silencing causes defective mitochondria clearance after uncoupler treatment. Moreover, pathogenic <jats:styled-content style=\"fixed-case\">VCP<\/jats:styled-content>s show impaired migration to mitochondria, and the exogenous pathogenic <jats:styled-content style=\"fixed-case\">VCP<\/jats:styled-content> expression partially inhibits Npl4 and p47 localization to mitochondria. These results suggest that the increased affinities of pathogenic <jats:styled-content style=\"fixed-case\">VCP<\/jats:styled-content>s for these cofactors cause the impaired movement of pathogenic <jats:styled-content style=\"fixed-case\">VCP<\/jats:styled-content>s. In adult flies, exogenous expression of wild\u2010type <jats:styled-content style=\"fixed-case\">VCP<\/jats:styled-content>, but not pathogenic <jats:styled-content style=\"fixed-case\">VCP<\/jats:styled-content>s, reduces the number of abnormal mitochondria in muscles. Failure of pathogenic <jats:styled-content style=\"fixed-case\">VCP<\/jats:styled-content>s to function on damaged mitochondria may be related to the pathogenesis of <jats:styled-content style=\"fixed-case\">IBMPFD<\/jats:styled-content> and <jats:styled-content style=\"fixed-case\">ALS<\/jats:styled-content>.<\/jats:p>","DOI":"10.1111\/gtc.12103","type":"journal-article","created":{"date-parts":[[2013,11,12]],"date-time":"2013-11-12T06:12:56Z","timestamp":1384236776000},"page":"1131-1143","source":"Crossref","is-referenced-by-count":39,"title":["Different dynamic movements of wild\u2010type and pathogenic <scp>VCP<\/scp>s and their cofactors to damaged mitochondria in a <scp>P<\/scp>arkin\u2010mediated mitochondrial quality control system"],"prefix":"10.1111","volume":"18","author":[{"given":"Yoko","family":"Kimura","sequence":"first","affiliation":[{"name":"Laboratory of Protein Metabolism Tokyo Metropolitan Institute of Medical Science Setagaya\u2010ku Tokyo 156\u20108506 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156\u20108506 Japan"},{"name":"Department of Medical Genome Sciences Graduate School of Frontier Sciences The University of Tokyo Kashiwa Chiba 277\u20108561 Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yukie","family":"Kakiyama","sequence":"additional","affiliation":[{"name":"Laboratory of Protein Metabolism Tokyo Metropolitan Institute of Medical Science Setagaya\u2010ku Tokyo 156\u20108506 Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Junko","family":"Kawawaki","sequence":"additional","affiliation":[{"name":"Laboratory of Protein Metabolism Tokyo Metropolitan Institute of Medical Science Setagaya\u2010ku Tokyo 156\u20108506 Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Akira","family":"Kakizuka","sequence":"additional","affiliation":[{"name":"Laboratory of Functional Biology Kyoto University Graduate School of Biostudies Kyoto 606\u20108501 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