{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,9]],"date-time":"2026-10-09T05:07:15Z","timestamp":1791522435369,"version":"4.3.4"},"reference-count":39,"publisher":"Oxford University Press (OUP)","issue":"4","license":[{"start":{"date-parts":[[2020,6,10]],"date-time":"2020-06-10T00:00:00Z","timestamp":1591747200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/journals\/pages\/open_access\/funder_policies\/chorus\/standard_publication_model"}],"funder":[{"name":"Grant-in-Aid for Scientific Research","award":["21390248"],"award-info":[{"award-number":["21390248"]}]},{"name":"Grant-in-Aid for Scientific Research","award":["22390157"],"award-info":[{"award-number":["22390157"]}]},{"name":"Grant-in-Aid for Scientific Research","award":["23132507"],"award-info":[{"award-number":["23132507"]}]},{"name":"Grant-in-Aid for Scientific Research","award":["23659414"],"award-info":[{"award-number":["23659414"]}]},{"name":"Grant-in-Aid for Scientific Research","award":["19590832"],"award-info":[{"award-number":["19590832"]}]},{"name":"Grant-in-Aid for Scientific Research","award":["16H05305"],"award-info":[{"award-number":["16H05305"]}]},{"name":"Grant-in-Aid for Scientific Research","award":["25293181"],"award-info":[{"award-number":["25293181"]}]},{"name":"Grant-in-Aid for Scientific Research","award":["16H05296"],"award-info":[{"award-number":["16H05296"]}]},{"DOI":"10.13039\/501100001700","name":"Ministry of Education, Culture, Sports, Science and Technology of Japan","doi-asserted-by":"crossref","id":[{"id":"10.13039\/501100001700","id-type":"DOI","asserted-by":"crossref"}]},{"name":"Ministry of Health, Labor and Welfare"},{"name":"Joint Usage\/Research Program of Medical Research Institute"},{"DOI":"10.13039\/501100007951","name":"Tokyo Medical and Dental University","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100007951","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2021,3,21]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:sec>\n                  <jats:title>Aims<\/jats:title>\n                  <jats:p>During heart failure, the levels of circulatory heat shock protein family D member 1 (HSP60) increase. However, its underlying mechanism is still unknown. The apical domain of heat shock protein family D member 1 (HSPD1) is conserved throughout evolution. We found a point mutation in HSPD1 in a familial dilated cardiomyopathy (DCM) patient. A similar point mutation in HSPD1 in the zebrafish mutant, nbl, led to loss of its regenerative capacity and development of pericardial oedema under heat stress condition. In this study, we aimed to determine the direct involvement of HSPD1 in the development of DCM.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Methods and results<\/jats:title>\n                  <jats:p>By Sanger method, we found a point mutation (Thr320Ala) in the apical domain of HSPD1, in one familial DCM patient, which was four amino acids away from the point mutation (Val324Glu) in the nbl mutant zebrafish. The nbl mutants showed atrio-ventricular block and sudden death at 8-month post-fertilization. Histological and microscopic analysis of the nbl mutant hearts showed decreased ventricular wall thickness, elevated level of reactive oxygen species (ROS), increased fibrosis, mitochondrial damage, and increased autophagosomes. mRNA and protein expression of autophagy-related genes significantly increased in nbl mutants. We established HEK293 stable cell lines of wild-type, nbl-type, and DCM-type HSPD1, with tetracycline-dependent expression. Compared to wild-type, both nbl- and DCM-type cells showed decreased cell growth, increased expression of ROS and autophagy-related genes, inhibition of the activity of mitochondrial electron transport chain complexes III and IV, and decreased mitochondrial fission and fusion.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Conclusion<\/jats:title>\n                  <jats:p>Mutations in HSPD1 caused mitochondrial dysfunction and induced mitophagy. Mitochondrial dysfunction caused increased ROS and cardiac atrophy.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1093\/cvr\/cvaa158","type":"journal-article","created":{"date-parts":[[2020,6,4]],"date-time":"2020-06-04T11:09:12Z","timestamp":1591268952000},"page":"1118-1131","source":"Crossref","is-referenced-by-count":35,"title":["Dilated cardiomyopathy-linked heat shock protein family D member 1 mutations cause up-regulation of reactive oxygen species and autophagy through mitochondrial dysfunction"],"prefix":"10.1093","volume":"117","author":[{"given":"Hirokazu","family":"Enomoto","sequence":"first","affiliation":[{"name":"Department of Cardiology, Keio University School of Medicine, Tokyo 160-8582, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nishant","family":"Mittal","sequence":"additional","affiliation":[{"name":"Department of Cardiology, Keio University School of Medicine, Tokyo 160-8582, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Takayuki","family":"Inomata","sequence":"additional","affiliation":[{"name":"Department of Cardiovascular Medicine, Kitasato University School of Medicine, Kanagawa 252-0374, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Takuro","family":"Arimura","sequence":"additional","affiliation":[{"name":"Department of Molecular Pathogenesis, Tokyo Medical and Dental University, Tokyo 113-8510, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tohru","family":"Izumi","sequence":"additional","affiliation":[{"name":"Department of Cardiovascular Medicine, Kitasato University School of Medicine, Kanagawa 252-0374, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Akinori","family":"Kimura","sequence":"additional","affiliation":[{"name":"Department of Molecular Pathogenesis, Tokyo Medical and Dental University, Tokyo 113-8510, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Keiichi","family":"Fukuda","sequence":"additional","affiliation":[{"name":"Department of Cardiology, Keio University School of Medicine, Tokyo 160-8582, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shinji","family":"Makino","sequence":"additional","affiliation":[{"name":"Department of Cardiology, Keio University School of Medicine, Tokyo 160-8582, Japan"},{"name":"Health Center, Keio University, Tokyo 160-8582, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2020,6,10]]},"reference":[{"key":"2021032208551761500_cvaa158-B1","doi-asserted-by":"crossref","first-page":"504","DOI":"10.1161\/01.CIR.83.2.504","article-title":"Impairment of the myocardial ultrastructure and changes of the cytoskeleton in dilated cardiomyopathy","volume":"83","author":"Schaper","year":"1991","journal-title":"Circulation"},{"key":"2021032208551761500_cvaa158-B2","doi-asserted-by":"crossref","first-page":"1756","DOI":"10.1253\/circj.CJ-11-0368","article-title":"Contribution of genetic factors to the pathogenesis of dilated cardiomyopathy: the cause of dilated cardiomyopathy: genetic or acquired? 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