{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,22]],"date-time":"2026-07-22T04:38:32Z","timestamp":1784695112058,"version":"3.55.0"},"reference-count":32,"publisher":"MDPI AG","issue":"11","license":[{"start":{"date-parts":[[2023,6,1]],"date-time":"2023-06-01T00:00:00Z","timestamp":1685577600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100003725","name":"National Research Foundation of Korea (NRF)","doi-asserted-by":"publisher","award":["2019R1A2C1086949"],"award-info":[{"award-number":["2019R1A2C1086949"]}],"id":[{"id":"10.13039\/501100003725","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003725","name":"National Research Foundation of Korea (NRF)","doi-asserted-by":"publisher","award":["2021R1I1A1A01046548"],"award-info":[{"award-number":["2021R1I1A1A01046548"]}],"id":[{"id":"10.13039\/501100003725","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003725","name":"National Research Foundation of Korea (NRF)","doi-asserted-by":"publisher","award":["2021R1A5A2031612"],"award-info":[{"award-number":["2021R1A5A2031612"]}],"id":[{"id":"10.13039\/501100003725","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003725","name":"Research Center for Controlling Intercellular Communication","doi-asserted-by":"publisher","award":["2019R1A2C1086949"],"award-info":[{"award-number":["2019R1A2C1086949"]}],"id":[{"id":"10.13039\/501100003725","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003725","name":"Research Center for Controlling Intercellular Communication","doi-asserted-by":"publisher","award":["2021R1I1A1A01046548"],"award-info":[{"award-number":["2021R1I1A1A01046548"]}],"id":[{"id":"10.13039\/501100003725","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003725","name":"Research Center for Controlling Intercellular Communication","doi-asserted-by":"publisher","award":["2021R1A5A2031612"],"award-info":[{"award-number":["2021R1A5A2031612"]}],"id":[{"id":"10.13039\/501100003725","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Bcl-2-interacting cell death suppressor (BIS), also called BAG3, plays a role in physiological functions such as anti-apoptosis, cell proliferation, autophagy, and senescence. Whole-body Bis-knockout (KO) mice exhibit early lethality accompanied by abnormalities in cardiac and skeletal muscles, suggesting the critical role of BIS in these muscles. In this study, we generated skeletal muscle-specific Bis-knockout (Bis-SMKO) mice for the first time. Bis-SMKO mice exhibit growth retardation, kyphosis, a lack of peripheral fat, and respiratory failure, ultimately leading to early death. Regenerating fibers and increased intensity in cleaved PARP1 immunostaining were observed in the diaphragm of Bis-SMKO mice, indicating considerable muscle degeneration. Through electron microscopy analysis, we observed myofibrillar disruption, degenerated mitochondria, and autophagic vacuoles in the Bis-SMKO diaphragm. Specifically, autophagy was impaired, and heat shock proteins (HSPs), such as HSPB5 and HSP70, and z-disk proteins, including filamin C and desmin, accumulated in Bis-SMKO skeletal muscles. We also found metabolic impairments, including decreased ATP levels and lactate dehydrogenase (LDH) and creatine kinase (CK) activities in the diaphragm of Bis-SMKO mice. Our findings highlight that BIS is critical for protein homeostasis and energy metabolism in skeletal muscles, suggesting that Bis-SMKO mice could be used as a therapeutic strategy for myopathies and to elucidate the molecular function of BIS in skeletal muscle physiology.<\/jats:p>","DOI":"10.3390\/ijms24119635","type":"journal-article","created":{"date-parts":[[2023,6,2]],"date-time":"2023-06-02T02:41:35Z","timestamp":1685673695000},"page":"9635","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Skeletal Muscle-Specific Bis Depletion Leads to Muscle Dysfunction and Early Death Accompanied by Impairment in Protein Quality Control"],"prefix":"10.3390","volume":"24","author":[{"given":"Soon-Young","family":"Jung","sequence":"first","affiliation":[{"name":"Department of Biochemistry, College of Medicine, The Catholic University of Korea, Seoul 06591, Republic of Korea"},{"name":"Institute for Aging and Metabolic Diseases, College of Medicine, The Catholic University of Korea, Seoul 06591, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tae-Ryong","family":"Riew","sequence":"additional","affiliation":[{"name":"Department of Anatomy, Catholic Neuroscience Institute, College of Medicine, The Catholic University of Korea, Seoul 06591, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hye Hyeon","family":"Yun","sequence":"additional","affiliation":[{"name":"Department of Biochemistry, College of Medicine, The Catholic University of Korea, Seoul 06591, Republic of Korea"},{"name":"Institute for Aging and Metabolic Diseases, College of Medicine, The Catholic University of Korea, Seoul 06591, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ji Hee","family":"Lim","sequence":"additional","affiliation":[{"name":"Division of Nephrology, Department of Internal Medicine, College of Medicine, The Catholic University of Korea, Seoul 06591, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9922-364X","authenticated-orcid":false,"given":"Ji-Won","family":"Hwang","sequence":"additional","affiliation":[{"name":"Department of Anatomy, Catholic Neuroscience Institute, College of Medicine, The Catholic University of Korea, Seoul 06591, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sung Won","family":"Jung","sequence":"additional","affiliation":[{"name":"Department of Anatomy, Catholic Neuroscience Institute, College of Medicine, The Catholic University of Korea, Seoul 06591, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hong Lim","family":"Kim","sequence":"additional","affiliation":[{"name":"Integrative Research Support Center, Laboratory of Electron Microscope, College of Medicine, The Catholic University of Korea, Seoul 06591, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6002-5267","authenticated-orcid":false,"given":"Jae-Seon","family":"Lee","sequence":"additional","affiliation":[{"name":"Research Center for Controlling Intercellular Communication (RCIC), College of Medicine, Inha University, Incheon 22212, Republic of Korea"},{"name":"Program in Biomedical Science & Engineering, Inha University, Incheon 22212, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mun-Yong","family":"Lee","sequence":"additional","affiliation":[{"name":"Department of Anatomy, Catholic Neuroscience Institute, College of Medicine, The Catholic University of Korea, Seoul 06591, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5970-194X","authenticated-orcid":false,"given":"Jeong-Hwa","family":"Lee","sequence":"additional","affiliation":[{"name":"Department of Biochemistry, College of Medicine, The Catholic University of Korea, Seoul 06591, Republic of Korea"},{"name":"Institute for Aging and Metabolic Diseases, College of Medicine, The Catholic University of Korea, Seoul 06591, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,6,1]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"6183","DOI":"10.1038\/sj.onc.1203043","article-title":"Bis, a Bcl-2-binding protein that synergizes with Bcl-2 in preventing cell death","volume":"18","author":"Lee","year":"1999","journal-title":"Oncogene"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"781","DOI":"10.1074\/jbc.274.2.781","article-title":"An evolutionarily conserved family of Hsp70\/Hsc70 molecular chaperone regulators","volume":"274","author":"Takayama","year":"1999","journal-title":"J. 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