{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,28]],"date-time":"2026-09-28T21:07:18Z","timestamp":1790629638955,"version":"4.1.0"},"reference-count":55,"publisher":"Wiley","issue":"12","license":[{"start":{"date-parts":[[2015,5,20]],"date-time":"2015-05-20T00:00:00Z","timestamp":1432080000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"name":"Japan Society for Promotion of Science (JSPS)","award":["9688"],"award-info":[{"award-number":["9688"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["The Journal of Physiology"],"published-print":{"date-parts":[[2015,6,15]]},"abstract":"<jats:sec><jats:title>Key points<\/jats:title><jats:p><jats:list list-type=\"bullet\">\n<jats:list-item><jats:p>Traumatic nerve injury or nerve disease leads to denervation and severe muscle atrophy. Recent evidence shows that mitochondrial loss could be a key mediator of skeletal muscle atrophy.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>Here, we show that daily heat stress treatment rescues denervation\u2010induced loss of mitochondria and concomitant muscle atrophy.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>We also found that denervation\u2010activated autophagy\u2010dependent mitochondrial clearance (mitophagy) was suppressed by daily heat stress treatment. The molecular basis of this observation is explained by our results showing that heat stress treatment attenuates the increase of key proteins that regulate the tagging step for mitochondrial clearance and the intermediate step of autophagosome formation in denervated muscle.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>These findings contribute to the better understanding of mitochondrial quality control in denervated muscle from a translational perspective and provide a mechanism behind the attenuation of muscle wasting by heat stress.<\/jats:p><\/jats:list-item>\n<\/jats:list><\/jats:p><\/jats:sec><jats:sec><jats:title>Abstract<\/jats:title><jats:p>Traumatic nerve injury or motor neuron disease leads to denervation and severe muscle atrophy. Recent evidence indicates that loss of mitochondria and the related reduction in oxidative capacity could be key mediators of skeletal muscle atrophy. As our previous study showed that heat stress increased the numbers of mitochondria in skeletal muscle, we evaluated whether heat stress treatment could have a beneficial impact on denervation\u2010induced loss of mitochondria and subsequent muscle atrophy. Here, we report that daily heat stress treatment (mice placed in a chamber with a hot environment; 40\u00b0C, 30\u00a0min\u00a0day<jats:sup>\u22121<\/jats:sup>, for 7\u00a0days) rescues the following parameters: (i)\u00a0muscle atrophy (decreased gastrocnemius muscle mass); (ii)\u00a0loss of mitochondrial content (decreased levels of ubiquinol\u2013cytochrome <jats:italic>c<\/jats:italic> reductase core protein\u00a0II, cytochrome <jats:italic>c<\/jats:italic> oxidase subunits\u00a0I and IV and voltage\u2010dependent anion channel protein); and (iii)\u00a0reduction in oxidative capacity (reduced maximal activities of citrate synthase and 3\u2010hydroxyacyl\u2010CoA dehydrogenase) in denervated muscle (produced by unilateral sciatic nerve transection). In order to gain a better understanding of the above mitochondrial adaptations, we also examined the effects of heat stress on autophagy\u2010dependent mitochondrial clearance (mitophagy). Daily heat stress normalized denervation\u2010activated induction of mitophagy (increased mitochondrial microtubule\u2010associated protein 1A\/1B\u2010light chain3\u2010II (LC3\u2010II) with and without blocker of autophagosome clearance). The molecular basis of this observation was explained by the results that heat stress attenuated the denervation\u2010induced increase in key proteins that regulate the following steps: (i)\u00a0the tagging step of mitochondrial clearance (increased mitochondrial Parkin, ubiquitin\u2010conjugated, P62\/sequestosome 1 (P62\/SQSTM1)); and (ii)\u00a0the elongation step of autophagosome formation (increased Atg5\u2013Atg12 conjugate and Atg16L). Overall, our results contribute to the better understanding of mitochondrial quality control and the mechanisms behind the attenuation of muscle wasting by heat stress in denervated skeletal muscle.<\/jats:p><\/jats:sec>","DOI":"10.1113\/jp270093","type":"journal-article","created":{"date-parts":[[2015,4,21]],"date-time":"2015-04-21T10:00:18Z","timestamp":1429610418000},"page":"2707-2720","source":"Crossref","is-referenced-by-count":74,"title":["Daily heat stress treatment rescues denervation\u2010activated mitochondrial clearance and atrophy in skeletal muscle"],"prefix":"10.1113","volume":"593","author":[{"given":"Yuki","family":"Tamura","sequence":"first","affiliation":[{"name":"Department of Sports Sciences The University of Tokyo  Tokyo Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yu","family":"Kitaoka","sequence":"additional","affiliation":[{"name":"Department of Sports Sciences The University of Tokyo  Tokyo Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yutaka","family":"Matsunaga","sequence":"additional","affiliation":[{"name":"Department of Sports Sciences The University of Tokyo  Tokyo Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daisuke","family":"Hoshino","sequence":"additional","affiliation":[{"name":"Department of Sports Sciences The University of Tokyo  Tokyo Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hideo","family":"Hatta","sequence":"additional","affiliation":[{"name":"Department of Sports Sciences The University of Tokyo  Tokyo Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2015,5,20]]},"reference":[{"key":"e_1_2_6_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbamcr.2011.08.007"},{"key":"e_1_2_6_3_1","doi-asserted-by":"publisher","DOI":"10.1038\/cdd.2012.81"},{"key":"e_1_2_6_4_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1432-1033.1969.tb00674.x"},{"key":"e_1_2_6_5_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M704332200"},{"key":"e_1_2_6_6_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature13418"},{"key":"e_1_2_6_7_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajpendo.00380.2013"},{"key":"e_1_2_6_8_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M110.113092"},{"key":"e_1_2_6_9_1","doi-asserted-by":"publisher","DOI":"10.1113\/jphysiol.2014.275545"},{"key":"e_1_2_6_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cmet.2013.03.015"},{"key":"e_1_2_6_11_1","doi-asserted-by":"publisher","DOI":"10.1158\/1535-7163.MCT-04-0322"},{"key":"e_1_2_6_12_1","doi-asserted-by":"publisher","DOI":"10.1113\/jphysiol.2008.167387"},{"key":"e_1_2_6_13_1","doi-asserted-by":"publisher","DOI":"10.2337\/db13-0665"},{"key":"e_1_2_6_14_1","doi-asserted-by":"publisher","DOI":"10.4161\/auto.27785"},{"key":"e_1_2_6_15_1","doi-asserted-by":"publisher","DOI":"10.3390\/cells1030325"},{"key":"e_1_2_6_16_1","doi-asserted-by":"publisher","DOI":"10.4062\/biomolther.2012.089"},{"key":"e_1_2_6_17_1","doi-asserted-by":"publisher","DOI":"10.2337\/db13-0967"},{"key":"e_1_2_6_18_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajpcell.2001.281.1.C179"},{"key":"e_1_2_6_19_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajpregu.00183.2011"},{"key":"e_1_2_6_20_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajpcell.00017.2014"},{"key":"e_1_2_6_21_1","doi-asserted-by":"publisher","DOI":"10.4161\/auto.6.7.12785"},{"key":"e_1_2_6_22_1","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.neuro.051508.135722"},{"key":"e_1_2_6_23_1","doi-asserted-by":"publisher","DOI":"10.1007\/s12576-013-0290-7"},{"key":"e_1_2_6_24_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI67615"},{"key":"e_1_2_6_25_1","doi-asserted-by":"publisher","DOI":"10.1038\/sj.onc.1208440"},{"key":"e_1_2_6_26_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajpregu.00046.2004"},{"key":"e_1_2_6_27_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature00904"},{"key":"e_1_2_6_28_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbagen.2009.07.031"},{"key":"e_1_2_6_29_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cmet.2012.10.005"},{"key":"e_1_2_6_30_1","doi-asserted-by":"publisher","DOI":"10.1242\/dmm.014126"},{"key":"e_1_2_6_31_1","doi-asserted-by":"publisher","DOI":"10.1002\/jcp.22871"},{"key":"e_1_2_6_32_1","doi-asserted-by":"publisher","DOI":"10.4161\/auto.6.2.11137"},{"key":"e_1_2_6_33_1","doi-asserted-by":"publisher","DOI":"10.1152\/japplphysiol.00591.2011"},{"key":"e_1_2_6_34_1","doi-asserted-by":"publisher","DOI":"10.4161\/auto.25955"},{"key":"e_1_2_6_35_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajpregu.00767.2006"},{"key":"e_1_2_6_36_1","doi-asserted-by":"publisher","DOI":"10.1152\/jappl.2000.88.1.359"},{"key":"e_1_2_6_37_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.tem.2013.09.004"},{"key":"e_1_2_6_38_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ebiom.2014.11.007"},{"key":"e_1_2_6_39_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajpcell.00240.2012"},{"key":"e_1_2_6_40_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajpcell.00451.2011"},{"key":"e_1_2_6_41_1","doi-asserted-by":"publisher","DOI":"10.1152\/japplphysiol.00739.2001"},{"key":"e_1_2_6_42_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajpendo.00609.2011"},{"key":"e_1_2_6_43_1","doi-asserted-by":"publisher","DOI":"10.1083\/jcb.200903131"},{"key":"e_1_2_6_44_1","doi-asserted-by":"publisher","DOI":"10.1038\/emboj.2010.60"},{"key":"e_1_2_6_45_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M110.211466"},{"key":"e_1_2_6_46_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0607795103"},{"key":"e_1_2_6_47_1","doi-asserted-by":"publisher","DOI":"10.1016\/0076-6879(69)13005-0"},{"key":"e_1_2_6_48_1","doi-asserted-by":"publisher","DOI":"10.1152\/japplphysiol.00471.2013"},{"key":"e_1_2_6_49_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajpregu.00525.2013"},{"key":"e_1_2_6_50_1","doi-asserted-by":"publisher","DOI":"10.1126\/scisignal.2004809"},{"key":"e_1_2_6_51_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.imr.2014.09.001"},{"key":"e_1_2_6_52_1","doi-asserted-by":"publisher","DOI":"10.1053\/j.gastro.2013.07.048"},{"key":"e_1_2_6_53_1","doi-asserted-by":"publisher","DOI":"10.1242\/jcs.131300"},{"key":"e_1_2_6_54_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajpcell.1991.260.4.C841"},{"key":"e_1_2_6_55_1","doi-asserted-by":"publisher","DOI":"10.2353\/ajpath.2009.080697"},{"key":"e_1_2_6_56_1","doi-asserted-by":"publisher","DOI":"10.1111\/apha.12040"}],"container-title":["The Journal of Physiology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1113%2FJP270093","content-type":"unspecified","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/physoc.onlinelibrary.wiley.com\/doi\/pdf\/10.1113\/JP270093","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,9,29]],"date-time":"2023-09-29T13:23:14Z","timestamp":1695993794000},"score":1,"resource":{"primary":{"URL":"https:\/\/physoc.onlinelibrary.wiley.com\/doi\/10.1113\/JP270093"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2015,5,20]]},"references-count":55,"journal-issue":{"issue":"12","published-print":{"date-parts":[[2015,6,15]]}},"alternative-id":["10.1113\/JP270093"],"URL":"https:\/\/doi.org\/10.1113\/jp270093","archive":["Portico"],"relation":{},"ISSN":["0022-3751","1469-7793"],"issn-type":[{"value":"0022-3751","type":"print"},{"value":"1469-7793","type":"electronic"}],"subject":[],"published":{"date-parts":[[2015,5,20]]}}}