{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,12]],"date-time":"2026-10-12T22:58:23Z","timestamp":1791845903855,"version":"4.3.4"},"reference-count":44,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2022,4,3]],"date-time":"2022-04-03T00:00:00Z","timestamp":1648944000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001691","name":"Japan Society for the Promotion of Science","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100001691","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["J cachexia sarcopenia muscle"],"published-print":{"date-parts":[[2022,6]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Sarcopenia is characterized by the loss of skeletal muscle mass and strength and is associated with poor prognosis in patients with chronic obstructive pulmonary disease (COPD). Cigarette smoke (CS) exposure, a major cause for COPD, induces mitochondrial damage, which has been implicated in sarcopenia pathogenesis. The current study sought to examine the involvement of insufficient Parkin\u2010mediated mitophagy, a mitochondrion\u2010selective autophagy, in the mechanisms by which dysfunctional mitochondria accumulate with excessive reactive oxygen species (ROS) production in the development of COPD\u2010related sarcopenia.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      The involvement of Parkin\u2010mediated mitophagy was examined using\n                      <jats:italic>in vitro<\/jats:italic>\n                      models of myotube formation,\n                      <jats:italic>in vivo<\/jats:italic>\n                      CS\u2010exposure model using Parkin\n                      <jats:sup>\u2212\/\u2212<\/jats:sup>\n                      mice, and human muscle samples from patients with COPD\u2010related sarcopenia.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Cigarette smoke extract (CSE) induced myotube atrophy with concomitant 30% reduction in Parkin expression levels (\n                      <jats:italic>P<\/jats:italic>\n                      \u00a0&lt;\u00a00.05). Parkin\u2010mediated mitophagy regulated myotube atrophy by modulating mitochondrial damage and mitochondrial ROS production. Increased mitochondrial ROS was responsible for myotube atrophy by activating Muscle Ring Finger 1 (MuRF\u20101)\u2010mediated myosin heavy chain (MHC) degradation. Parkin\n                      <jats:sup>\u2212\/\u2212<\/jats:sup>\n                      mice with prolonged CS exposure showed enhanced limb muscle atrophy with a 31.7% reduction in limb muscle weights (\n                      <jats:italic>P<\/jats:italic>\n                      \u00a0&lt;\u00a00.01) and 2.3 times greater MuRF\u20101 expression (\n                      <jats:italic>P<\/jats:italic>\n                      \u00a0&lt;\u00a00.01) compared with wild\u2010type mice with concomitant accumulation of damaged mitochondria and oxidative modifications in 4HNE expression. Patients with COPD\u2010related sarcopenia exhibited significantly reduced Parkin but increased MuRF\u20101 protein levels (35% lower and 2.5 times greater protein levels compared with control patients,\n                      <jats:italic>P<\/jats:italic>\n                      \u00a0&lt;\u00a00.01 and\n                      <jats:italic>P<\/jats:italic>\n                      \u00a0&lt;\u00a00.05, respectively) and damaged mitochondria accumulation demonstrated in muscles. Electric pulse stimulation\u2010induced muscle contraction prevented CSE\u2010induced MHC reduction by maintaining Parkin levels in myotubes.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Taken together, COPD\u2010related sarcopenia can be attributed to insufficient Parkin\u2010mediated mitophagy and increased mitochondrial ROS causing enhanced muscle atrophy through MuRF\u20101 activation, which may be at least partly preventable through optimal physical exercise.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/jcsm.12988","type":"journal-article","created":{"date-parts":[[2022,4,3]],"date-time":"2022-04-03T22:15:20Z","timestamp":1649024120000},"page":"1864-1882","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":59,"title":["Involvement of Parkin\u2010mediated mitophagy in the pathogenesis of chronic obstructive pulmonary disease\u2010related sarcopenia"],"prefix":"10.1002","volume":"13","author":[{"given":"Akihiko","family":"Ito","sequence":"first","affiliation":[{"name":"Division of Respiratory Diseases, Department of Internal Medicine The Jikei University  Tokyo Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4817-2210","authenticated-orcid":false,"given":"Mitsuo","family":"Hashimoto","sequence":"additional","affiliation":[{"name":"Division of Respiratory Diseases, Department of Internal Medicine The Jikei University  Tokyo Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jun","family":"Tanihata","sequence":"additional","affiliation":[{"name":"Department of Cell Physiology The Jikei University  Tokyo Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sachi","family":"Matsubayashi","sequence":"additional","affiliation":[{"name":"Division of Respiratory Diseases, 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