{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,15]],"date-time":"2026-10-15T05:34:48Z","timestamp":1792042488123,"version":"4.4.0"},"reference-count":50,"publisher":"National Academy of Sciences","issue":"4","license":[{"start":{"date-parts":[[2023,1,17]],"date-time":"2023-01-17T00:00:00Z","timestamp":1673913600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100000923","name":"Department of Education and Training | Australian Research Council","doi-asserted-by":"publisher","award":["DP220102018"],"award-info":[{"award-number":["DP220102018"]}],"id":[{"id":"10.13039\/501100000923","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["www.pnas.org"],"crossmark-restriction":true},"short-container-title":["Proc. Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[2023,1,24]]},"abstract":"<jats:p>\n                    Resting skeletal muscle generates heat for endothermy in mammals but not amphibians, while both use the same Ca\n                    <jats:sup>2+<\/jats:sup>\n                    -handling proteins and membrane structures to conduct excitation\u2013contraction coupling apart from having different ryanodine receptor (RyR) isoforms for Ca\n                    <jats:sup>2+<\/jats:sup>\n                    release. The sarcoplasmic reticulum (SR) generates heat following Adenosine triphosphate (ATP) hydrolysis at the Ca\n                    <jats:sup>2+<\/jats:sup>\n                    pump, which is amplified by increasing RyR1 Ca\n                    <jats:sup>2+<\/jats:sup>\n                    leak in mammals, subsequently increasing cytoplasmic [Ca\n                    <jats:sup>2+<\/jats:sup>\n                    ] ([Ca\n                    <jats:sup>2+<\/jats:sup>\n                    ]\n                    <jats:sub>cyto<\/jats:sub>\n                    ). For thermogenesis to be functional, rising [Ca\n                    <jats:sup>2+<\/jats:sup>\n                    ]\n                    <jats:sub>cyto<\/jats:sub>\n                    must not interfere with cytoplasmic effectors of the sympathetic nervous system (SNS) that likely increase RyR1 Ca\n                    <jats:sup>2+<\/jats:sup>\n                    leak; nor should it compromise the muscle remaining relaxed. To achieve this, Ca\n                    <jats:sup>2+<\/jats:sup>\n                    activated, regenerative Ca\n                    <jats:sup>2+<\/jats:sup>\n                    release that is robust in lower vertebrates needs to be suppressed in mammals. However, it has not been clear whether: i) the RyR1 can be opened by local increases in [Ca\n                    <jats:sup>2+<\/jats:sup>\n                    ]\n                    <jats:sub>cyto<\/jats:sub>\n                    ; and ii) downstream effectors of the SNS increase RyR Ca\n                    <jats:sup>2+<\/jats:sup>\n                    leak and subsequently, heat generation. By positioning amphibian and malignant hyperthermia-susceptible human-skinned muscle fibers perpendicularly, we induced abrupt rises in [Ca\n                    <jats:sup>2+<\/jats:sup>\n                    ]\n                    <jats:sub>cyto<\/jats:sub>\n                    under identical conditions optimized for activating regenerative Ca\n                    <jats:sup>2+<\/jats:sup>\n                    release as Ca\n                    <jats:sup>2+<\/jats:sup>\n                    waves passed through the junction of fibers. Only mammalian fibers showed resistance to rising [Ca\n                    <jats:sup>2+<\/jats:sup>\n                    ]\n                    <jats:sub>cyto<\/jats:sub>\n                    , resulting in increased SR Ca\n                    <jats:sup>2+<\/jats:sup>\n                    load and leak. Fiber heat output was increased by cyclic adenosine monophosphate (cAMP)-induced RyR1 phosphorylation at Ser2844 and Ca\n                    <jats:sup>2+<\/jats:sup>\n                    leak, indicating likely SNS regulation of thermogenesis. Thermogenesis occurred despite the absence of SR Ca\n                    <jats:sup>2+<\/jats:sup>\n                    pump regulator sarcolipin. Thus, evolutionary isolation of RyR1 provided increased dynamic range for thermogenesis with sensitivity to cAMP, supporting endothermy.\n                  <\/jats:p>","DOI":"10.1073\/pnas.2117503120","type":"journal-article","created":{"date-parts":[[2023,1,17]],"date-time":"2023-01-17T16:46:31Z","timestamp":1673973991000},"update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":17,"title":["Evolutionary isolation of ryanodine receptor isoform 1 for muscle-based thermogenesis in mammals"],"prefix":"10.1073","volume":"120","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4868-2501","authenticated-orcid":false,"given":"Daniel P.","family":"Singh","sequence":"first","affiliation":[{"name":"School of Biomedical Sciences, The University of Queensland, Brisbane, QLD 4072, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9369-1511","authenticated-orcid":false,"given":"Luke","family":"Pearce","sequence":"additional","affiliation":[{"name":"School of Biomedical Sciences, The University of Queensland, Brisbane, QLD 4072, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rocky H.","family":"Choi","sequence":"additional","affiliation":[{"name":"School of Biomedical Sciences, The University of Queensland, Brisbane, QLD 4072, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aldo","family":"Meizoso-Huesca","sequence":"additional","affiliation":[{"name":"School of Biomedical Sciences, The University of Queensland, Brisbane, QLD 4072, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6099-8445","authenticated-orcid":false,"given":"Stefan G.","family":"Wette","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Chemistry, La Trobe Institute for Molecular Science, School of Agriculture, Biomedicine and Environment, La Trobe University, Melbourne, VIC 3083, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John W.","family":"Scott","sequence":"additional","affiliation":[{"name":"Drug Discovery Biology Unit, Monash Institute of Pharmaceutical Sciences, Monash University, Melbourne, VIC 3052, Australia"},{"name":"The Florey Institute of Neuroscience and Mental Health, Melbourne, VIC 3052, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cedric R.","family":"Lamboley","sequence":"additional","affiliation":[{"name":"School of Biomedical Sciences, The University of Queensland, Brisbane, QLD 4072, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robyn M.","family":"Murphy","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Chemistry, La Trobe Institute for Molecular Science, School of Agriculture, Biomedicine and Environment, La Trobe University, Melbourne, VIC 3083, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0700-4867","authenticated-orcid":false,"given":"Bradley S.","family":"Launikonis","sequence":"additional","affiliation":[{"name":"School of Biomedical Sciences, The University of Queensland, Brisbane, QLD 4072, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"341","published-online":{"date-parts":[[2023,1,17]]},"reference":[{"key":"e_1_3_4_1_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.2119203119"},{"key":"e_1_3_4_2_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1800490115"},{"key":"e_1_3_4_3_2","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.ph.56.030194.002535"},{"key":"e_1_3_4_4_2","doi-asserted-by":"publisher","DOI":"10.1038\/nm.2897"},{"key":"e_1_3_4_5_2","doi-asserted-by":"publisher","DOI":"10.1096\/fasebj.9.5.7896003"},{"key":"e_1_3_4_6_2","doi-asserted-by":"publisher","DOI":"10.1152\/physrev.00016.2016"},{"key":"e_1_3_4_7_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M005809200"},{"key":"e_1_3_4_8_2","doi-asserted-by":"publisher","DOI":"10.1016\/0304-4157(94)00014-5"},{"key":"e_1_3_4_9_2","doi-asserted-by":"publisher","DOI":"10.1046\/j.1440-1681.2000.03224.x"},{"key":"e_1_3_4_10_2","doi-asserted-by":"publisher","DOI":"10.1085\/jgp.201711959"},{"key":"e_1_3_4_11_2","doi-asserted-by":"publisher","DOI":"10.1152\/physrev.00040.2008"},{"key":"e_1_3_4_12_2","doi-asserted-by":"publisher","DOI":"10.1113\/JP274515"},{"key":"e_1_3_4_13_2","doi-asserted-by":"publisher","DOI":"10.14814\/phy2.14921"},{"key":"e_1_3_4_14_2","doi-asserted-by":"publisher","DOI":"10.1085\/jgp.107.1.1"},{"key":"e_1_3_4_15_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1469-7793.1998.377be.x"},{"key":"e_1_3_4_16_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1469-7793.1999.00483.x"},{"key":"e_1_3_4_17_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1469-7793.2000.00299.x"},{"key":"e_1_3_4_18_2","doi-asserted-by":"publisher","DOI":"10.1113\/jphysiol.2014.274274"},{"key":"e_1_3_4_19_2","doi-asserted-by":"publisher","DOI":"10.1113\/jphysiol.1991.sp018771"},{"key":"e_1_3_4_20_2","doi-asserted-by":"publisher","DOI":"10.1113\/jphysiol.1996.sp021388"},{"key":"e_1_3_4_21_2","doi-asserted-by":"publisher","DOI":"10.1007\/s10974-019-09547-5"},{"key":"e_1_3_4_22_2","doi-asserted-by":"crossref","unstructured":"C. R. Lamboley Ryanodine receptor leak triggers fibre Ca2+ redistribution to preserve force and elevate basal metabolism in skeletal muscle. Sci. Adv. 7 eabi7144 (2021). eabi7144","DOI":"10.1126\/sciadv.abi7166"},{"key":"e_1_3_4_23_2","doi-asserted-by":"publisher","DOI":"10.1113\/jphysiol.2005.087973"},{"key":"e_1_3_4_24_2","doi-asserted-by":"publisher","DOI":"10.1038\/415198a"},{"key":"e_1_3_4_25_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.bja.2018.07.008"},{"key":"e_1_3_4_26_2","doi-asserted-by":"publisher","DOI":"10.1152\/japplphysiol.00445.2018"},{"key":"e_1_3_4_27_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1469-7793.1997.003bl.x"},{"key":"e_1_3_4_28_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0006-3495(00)76731-2"},{"key":"e_1_3_4_29_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.pbiomolbio.2010.10.003"},{"key":"e_1_3_4_30_2","doi-asserted-by":"publisher","DOI":"10.1038\/228034a0"},{"key":"e_1_3_4_31_2","doi-asserted-by":"publisher","DOI":"10.1113\/jphysiol.2011.225854"},{"key":"e_1_3_4_32_2","first-page":"E181","article-title":"Sympathoadrenal system and regulation of thermogenesis","volume":"247","author":"Landsberg L.","year":"1984","unstructured":"L. Landsberg, M. E. Saville, J. B. Young, Sympathoadrenal system and regulation of thermogenesis. Am. J. Physiol. 247, E181\u2013E189 (1984).","journal-title":"Am. J. Physiol."},{"key":"e_1_3_4_33_2","doi-asserted-by":"publisher","DOI":"10.1152\/physrev.00028.2007"},{"key":"e_1_3_4_34_2","doi-asserted-by":"publisher","DOI":"10.1113\/JP270909"},{"key":"e_1_3_4_35_2","doi-asserted-by":"publisher","DOI":"10.1152\/ajpcell.1995.268.5.C1313"},{"key":"e_1_3_4_36_2","doi-asserted-by":"crossref","unstructured":"L. Pearce Ryanodine receptor activity and store-operated Ca 2+ entry: Critical regulators of Ca 2+ content and function in skeletal muscle. J. Physiol. 10.1113\/JP279512 (2022).","DOI":"10.1113\/JP279512"},{"key":"e_1_3_4_37_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1469-7793.2001.0499f.x"},{"key":"e_1_3_4_38_2","doi-asserted-by":"crossref","unstructured":"C. J. Barclay B. S. Launikonis A mathematical model to quantify RYR Ca2+ leak and associated heat production in resting human skeletal muscle fibers. J. Gen. Physiol. 154 e202112994 (2022). e202112994","DOI":"10.1085\/jgp.202112994"},{"key":"e_1_3_4_39_2","doi-asserted-by":"publisher","DOI":"10.3389\/fphys.2021.633058"},{"key":"e_1_3_4_40_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1619835114"},{"key":"e_1_3_4_41_2","doi-asserted-by":"publisher","DOI":"10.1152\/ajpcell.00364.2020"},{"key":"e_1_3_4_42_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbamcr.2019.02.014"},{"key":"e_1_3_4_43_2","doi-asserted-by":"publisher","DOI":"10.1085\/jgp.201711889"},{"key":"e_1_3_4_44_2","doi-asserted-by":"publisher","DOI":"10.1085\/jgp.201812152"},{"key":"e_1_3_4_45_2","doi-asserted-by":"publisher","DOI":"10.1152\/ajpcell.00092.2022"},{"key":"e_1_3_4_46_2","doi-asserted-by":"publisher","DOI":"10.1177\/0310057X1504300204"},{"key":"e_1_3_4_47_2","doi-asserted-by":"publisher","DOI":"10.1038\/ncomms14266"},{"key":"e_1_3_4_48_2","doi-asserted-by":"publisher","DOI":"10.1113\/JP271658"},{"key":"e_1_3_4_49_2","doi-asserted-by":"publisher","DOI":"10.1038\/srep06701"},{"key":"e_1_3_4_50_2","doi-asserted-by":"publisher","DOI":"10.1113\/jphysiol.2008.163162"}],"container-title":["Proceedings of the National Academy of Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/pnas.org\/doi\/pdf\/10.1073\/pnas.2117503120","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,9,21]],"date-time":"2023-09-21T08:46:54Z","timestamp":1695286014000},"score":1,"resource":{"primary":{"URL":"https:\/\/pnas.org\/doi\/10.1073\/pnas.2117503120"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,1,17]]},"references-count":50,"journal-issue":{"issue":"4","published-print":{"date-parts":[[2023,1,24]]}},"alternative-id":["10.1073\/pnas.2117503120"],"URL":"https:\/\/doi.org\/10.1073\/pnas.2117503120","relation":{},"ISSN":["0027-8424","1091-6490"],"issn-type":[{"value":"0027-8424","type":"print"},{"value":"1091-6490","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,1,17]]},"assertion":[{"value":"2021-09-23","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2022-12-05","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2023-01-17","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e2117503120"}}