{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T14:49:26Z","timestamp":1785422966331,"version":"3.56.0"},"reference-count":34,"publisher":"The Company of Biologists","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"abstract":"<jats:p>Muscle differentiation requires a complex signaling cascade that leads to multinucleated myofibers. Genes regulating the intrinsic mitochondrial apoptotic pathway also function in controlling cell differentiation. How such signaling pathways are regulated during differentiation is not fully understood. Bit-1 mutations in humans cause infantile-onset multisystem disease with muscle weakness. We demonstrate here that Bit-1 controls skeletal myogenesis through a caspase-mediated signaling pathway. Bit-1 null mice exhibit a myopathy with hypotrophic myofibers. Bit-1 null myoblasts prematurely express muscle-specific proteins. Similarly, knockdown of Bit-1 expression in C2C12 myoblasts promotes early differentiation whereas overexpression delays differentiation. In wild type mice Bit-1 levels increase during differentiation. Bit-1 null myoblasts exhibited increased caspase 9 and caspase 3 without increased apoptosis*. Bit-1 re-expression partially rescued differentiation. In Bit-1 null muscle, Bcl-2 is reduced suggesting Bcl-2-mediated inhibition of caspase 9 and caspase 3 is decreased. Bcl-2 re-expression rescued Bit-1-mediated early differentiation in Bit-1 null myoblasts and C2C12s with knockdown of Bit-1 expression. These results support an unanticipated yet essential role for Bit-1 in controlling myogenesis through regulation of Bcl-2.<\/jats:p>","DOI":"10.1242\/jcs.158964","type":"journal-article","created":{"date-parts":[[2015,3,14]],"date-time":"2015-03-14T01:33:30Z","timestamp":1426296810000},"source":"Crossref","is-referenced-by-count":11,"title":["Bit-1 is an essential regulator of myogenic differentiation"],"prefix":"10.1242","author":[{"given":"Genevieve S.","family":"Griffiths","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jinger","family":"Doe","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mayumi","family":"Jijiwa","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pam","family":"Van Ry","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vivian","family":"Cruz","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michelle","family":"de la Vega","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joe W.","family":"Ramos","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dean J.","family":"Burkin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michelle L.","family":"Matter","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"237","published-online":{"date-parts":[[2015,1,1]]},"reference":[{"key":"2021042613484737100_b01","doi-asserted-by":"publisher","first-page":"13","DOI":"10.1139\/o98--007","article-title":"Murray L. 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