{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,21]],"date-time":"2026-09-21T23:16:06Z","timestamp":1790032566739,"version":"4.0.1"},"reference-count":34,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2017,9,20]],"date-time":"2017-09-20T00:00:00Z","timestamp":1505865600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"name":"Duchenne Alliance","award":["100065"],"award-info":[{"award-number":["100065"]}]},{"name":"Duchenne Alliance","award":["100071"],"award-info":[{"award-number":["100071"]}]},{"name":"Ryan's Quest"},{"name":"Hope for Gus"},{"name":"Team Joseph"},{"name":"Michael's Cause"},{"name":"Duchenne Now"},{"name":"Zack Heger Foundation"},{"name":"Pietro's Fight"},{"name":"RaceMD"},{"name":"JB's Keys"},{"name":"Romito Foundation"},{"name":"Harrison's Fund"},{"name":"Alex's Wish"},{"name":"Two Smiles One Hope Foundation"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Acta Physiologica"],"published-print":{"date-parts":[[2018,2]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Aim<\/jats:title><jats:p>Duchenne muscular dystrophy is caused by the absence of functional dystrophin protein and results in a host of secondary effects. Emerging evidence suggests that dystrophic pathology includes decreased pro\u2010autophagic signalling and suppressed autophagic flux in skeletal muscle, but the relationship between autophagy and disease progression is unknown. The purpose of this investigation was to determine the extent to which basal autophagy changes with disease progression. We hypothesized that autophagy impairment would increase with advanced disease.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>To test this hypothesis, 7\u2010week\u2010old and 17\u2010month\u2010old dystrophic diaphragms were compared to each other and age\u2010matched controls.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Changes in protein markers of autophagy indicate impaired autophagic stimulation through AMPK, however, robust pathway activation in dystrophic muscle, independent of disease severity. Relative protein abundance of p62, an inverse correlate of autophagic degradation, was dramatically elevated with disease regardless of age. Likewise, relative protein abundance of Lamp2, a lysosome marker, was decreased twofold at 17 months of age in dystrophic muscle and was confirmed, along with mislocalization, in histological samples, implicating lysosomal dysregulation in this process. In dystrophic muscle, autophagosome\u2010sized p62\u2010positive foci were observed in the extracellular space. Moreover, we found that autophagosomes were released from both healthy and dystrophic diaphragms into the extracellular environment, and the occurrence of autophagosome escape was more frequent in dystrophic muscle.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>These findings suggest autophagic dysfunction proceeds independent of disease progression and blunted degradation of autophagosomes is due in part to decreased lysosome abundance, and contributes to autophagosomal escape to the extracellular space.<\/jats:p><\/jats:sec>","DOI":"10.1111\/apha.12944","type":"journal-article","created":{"date-parts":[[2017,8,19]],"date-time":"2017-08-19T10:06:34Z","timestamp":1503137194000},"source":"Crossref","is-referenced-by-count":33,"title":["Autophagic dysfunction and autophagosome escape in the mdx <i>mus musculus<\/i> model of Duchenne muscular dystrophy"],"prefix":"10.1111","volume":"222","author":[{"given":"H. R.","family":"Spaulding","sequence":"first","affiliation":[{"name":"Department of Animal Science Iowa State University Ames IA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"E. M.","family":"Kelly","sequence":"additional","affiliation":[{"name":"Coriell Institute for Medical Research Camden NJ USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J. C.","family":"Quindry","sequence":"additional","affiliation":[{"name":"Department of Health and Human Performance University of Montana Missoula MT USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J. B.","family":"Sheffield","sequence":"additional","affiliation":[{"name":"Department of Biology Temple University Philadelphia PA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M. B.","family":"Hudson","sequence":"additional","affiliation":[{"name":"Department of Kinesiology and Applied Physiology University of Delaware Newark DE USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J. T.","family":"Selsby","sequence":"additional","affiliation":[{"name":"Department of Animal Science Iowa State University Ames IA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2017,9,20]]},"reference":[{"key":"e_1_2_8_2_1","doi-asserted-by":"publisher","DOI":"10.1152\/japplphysiol.01283.2009"},{"key":"e_1_2_8_3_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.275.13.9452"},{"key":"e_1_2_8_4_1","doi-asserted-by":"publisher","DOI":"10.1113\/expphysiol.2010.054379"},{"key":"e_1_2_8_5_1","doi-asserted-by":"publisher","DOI":"10.1113\/jphysiol.2012.240390"},{"key":"e_1_2_8_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.redox.2015.01.003"},{"key":"e_1_2_8_7_1","doi-asserted-by":"publisher","DOI":"10.1242\/jcs.114041"},{"key":"e_1_2_8_8_1","doi-asserted-by":"publisher","DOI":"10.3390\/cells1030325"},{"key":"e_1_2_8_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajpath.2012.04.004"},{"key":"e_1_2_8_10_1","doi-asserted-by":"publisher","DOI":"10.1038\/ncomms5425"},{"key":"e_1_2_8_11_1","doi-asserted-by":"publisher","DOI":"10.1038\/ncb2152"},{"key":"e_1_2_8_12_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cmet.2007.11.004"},{"key":"e_1_2_8_13_1","doi-asserted-by":"publisher","DOI":"10.1038\/cddis.2012.159"},{"key":"e_1_2_8_14_1","doi-asserted-by":"publisher","DOI":"10.1038\/cdd.2016.70"},{"key":"e_1_2_8_15_1","doi-asserted-by":"publisher","DOI":"10.1113\/JP272057"},{"key":"e_1_2_8_16_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0168293"},{"key":"e_1_2_8_17_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajpcell.00183.2011"},{"key":"e_1_2_8_18_1","doi-asserted-by":"publisher","DOI":"10.1038\/ncb2797"},{"key":"e_1_2_8_19_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.molcel.2011.07.039"},{"key":"e_1_2_8_20_1","doi-asserted-by":"publisher","DOI":"10.1247\/csf.27.421"},{"key":"e_1_2_8_21_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.1204592"},{"key":"e_1_2_8_22_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajpcell.00266.2013"},{"key":"e_1_2_8_23_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajpcell.00395.2013"},{"key":"e_1_2_8_24_1","doi-asserted-by":"publisher","DOI":"10.1080\/15548627.2015.1100356"},{"key":"e_1_2_8_25_1","doi-asserted-by":"publisher","DOI":"10.1096\/fj.13-237388"},{"key":"e_1_2_8_26_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.molcel.2011.06.038"},{"key":"e_1_2_8_27_1","doi-asserted-by":"publisher","DOI":"10.1038\/aps.2013.12"},{"key":"e_1_2_8_28_1","doi-asserted-by":"publisher","DOI":"10.1038\/cr.2013.11"},{"key":"e_1_2_8_29_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.yexcr.2006.04.024"},{"key":"e_1_2_8_30_1","doi-asserted-by":"publisher","DOI":"10.1002\/jcp.20696"},{"key":"e_1_2_8_31_1","doi-asserted-by":"publisher","DOI":"10.1080\/2162402X.2016.1180485"},{"key":"e_1_2_8_32_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature18928"},{"key":"e_1_2_8_33_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1404651111"},{"key":"e_1_2_8_34_1","doi-asserted-by":"crossref","first-page":"398","DOI":"10.1177\/1087057110364242","article-title":"A live\u2010cell fluorescence microplate assay suitable for monitoring vacuolation arising from drug or toxic agent treatment","volume":"15","author":"Coleman J","year":"2010","journal-title":"J Biomol Screen"},{"key":"e_1_2_8_35_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2010.01.028"}],"container-title":["Acta Physiologica"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1111%2Fapha.12944","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/apha.12944","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,9,27]],"date-time":"2023-09-27T19:48:26Z","timestamp":1695844106000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/apha.12944"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2017,9,20]]},"references-count":34,"journal-issue":{"issue":"2","published-print":{"date-parts":[[2018,2]]}},"alternative-id":["10.1111\/apha.12944"],"URL":"https:\/\/doi.org\/10.1111\/apha.12944","archive":["Portico"],"relation":{},"ISSN":["1748-1708","1748-1716"],"issn-type":[{"value":"1748-1708","type":"print"},{"value":"1748-1716","type":"electronic"}],"subject":[],"published":{"date-parts":[[2017,9,20]]},"article-number":"e12944"}}