{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,12]],"date-time":"2026-06-12T06:19:59Z","timestamp":1781245199812,"version":"3.54.1"},"reference-count":49,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2019,9,13]],"date-time":"2019-09-13T00:00:00Z","timestamp":1568332800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Physiol."],"DOI":"10.3389\/fphys.2019.01142","type":"journal-article","created":{"date-parts":[[2019,9,13]],"date-time":"2019-09-13T09:42:16Z","timestamp":1568367736000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":24,"title":["Excessive Accumulation of Ca2 + in Mitochondria of Y522S-RYR1 Knock-in Mice: A Link Between Leak From the Sarcoplasmic Reticulum and Altered Redox State"],"prefix":"10.3389","volume":"10","author":[{"given":"Marta","family":"Canato","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paola","family":"Capitanio","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lina","family":"Cancellara","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Luigi","family":"Leanza","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anna","family":"Raffaello","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Denis Vecellio","family":"Reane","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lorenzo","family":"Marcucci","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Antonio","family":"Michelucci","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Feliciano","family":"Protasi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carlo","family":"Reggiani","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2019,9,13]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"4531","DOI":"10.1073\/pnas.0812661106","article-title":"A retrograde signal from RyR1 alters DHP receptor inactivation and limits window Ca2+ release in muscle fibers of Y522S RyR1 knock-in mice.","volume":"106","author":"Andronache","year":"2009","journal-title":"Proc. Natl. Acad. Sci. U.S.A."},{"key":"B2","doi-asserted-by":"publisher","first-page":"40354","DOI":"10.174\/jbc","article-title":"Identification of cysteines involved in S-nitrosylation, S-glutathionylation, and oxidation to disulfides in ryanodine receptor type 1.","volume":"281","author":"Aracena-Parks","year":"2006","journal-title":"J. Biol. Chem."},{"key":"B3","doi-asserted-by":"publisher","DOI":"10.1177\/1744806918797032","article-title":"Mitochondrial superoxide increases excitatory synaptic strength in spinal dorsal horn neurons of neuropathic mice.","volume":"14","author":"Bae","year":"2018","journal-title":"Mol. Pain"},{"key":"B4","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-017-14134-0","article-title":"Exercise-dependent formation of new junctions that promote STIM1-Orai1 assemblyin skeletal muscle.","volume":"7","author":"Boncompagni","year":"2017","journal-title":"Sci. Rep."},{"key":"B5","doi-asserted-by":"publisher","first-page":"21996","DOI":"10.1073\/pnas.0911496106","article-title":"Characterization, and temporal development of cores in a mouse model of malignant hyperthermia.","volume":"106","author":"Boncompagni","year":"","journal-title":"Proc. Natl. Acad. Sci. U.S.A."},{"key":"B6","doi-asserted-by":"publisher","first-page":"1058","DOI":"10.1091\/mbc.E08-07-0783","article-title":"Mitochondria are linked to calcium stores in striated muscle by developmentally regulated tethering structures.","volume":"20","author":"Boncompagni","year":"","journal-title":"MolBiol. Cell."},{"key":"B7","doi-asserted-by":"publisher","first-page":"22326","DOI":"10.1073\/pnas.1009168108","article-title":"Massivealterations of sarcoplasmic reticulum free calcium in skeletal muscle fiberslackingcalsequestrin revealed by a genetically encoded probe.","volume":"107","author":"Canato","year":"2010","journal-title":"Proc. Natl. Acad. Sci. U.S.A."},{"key":"B8","doi-asserted-by":"publisher","first-page":"329","DOI":"10.1096\/fj.05-4497fje","article-title":"Heat- and anesthesia-induced malignant hyperthermia in an RyR1 knock-in mouse.","volume":"20","author":"Chelu","year":"2006","journal-title":"FASEB J."},{"key":"B9","doi-asserted-by":"publisher","first-page":"160","DOI":"10.1016\/j.cell.2013.08.032","article-title":"Mitochondrial cristae shape determines respiratory chain supercomplexes assembly and respiratory efficiency.","volume":"155","author":"Cogliati","year":"2013","journal-title":"Cell"},{"key":"B10","doi-asserted-by":"publisher","first-page":"7341","DOI":"10.1113\/JP272796","article-title":"Hyperammonaemia-induced skeletal muscle mitochondrial dysfunction results in cataplerosis and oxidative stress.","volume":"594","author":"Davuluri","year":"2016","journal-title":"J. Physiol."},{"key":"B11","doi-asserted-by":"publisher","first-page":"27","DOI":"10.1002\/jemt.20177","article-title":"Imaging and elasticity measurements of the sarcolemma of fully differentiated skeletal muscle fibres.","volume":"67","author":"Defranchi","year":"2005","journal-title":"Microsc. Res. Tech."},{"key":"B12","doi-asserted-by":"publisher","first-page":"1309","DOI":"10.1016\/j.bbabio.2009.01.005","article-title":"Regulation of mitochondrial dehydrogenases by calcium ions.","volume":"1787","author":"Denton","year":"2009","journal-title":"Biochim. Biophys. Acta"},{"key":"B13","doi-asserted-by":"publisher","first-page":"25645","DOI":"10.1074\/jbc.M110.104976","article-title":"Store-operated Ca2+ entry in malignant hyperthermia-susceptible human skeletal muscle.","volume":"285","author":"Duke","year":"2010","journal-title":"J. Biol. Chem."},{"key":"B14","doi-asserted-by":"publisher","first-page":"53","DOI":"10.1016\/j.cell.2008.02.042","article-title":"RyR1 S-nitrosylation underlies environmental heat stroke, and sudden death inY522S RyR1 knockin mice.","volume":"133","author":"Durham","year":"2008","journal-title":"Cell"},{"key":"B15","doi-asserted-by":"publisher","first-page":"991","DOI":"10.1096\/fj.12-218354","article-title":"Nonspecific sarcolemmalcation channels are critical for the pathogenesis of malignant hyperthermia.","volume":"27","author":"Eltit","year":"2013","journal-title":"FASEB J."},{"key":"B16","doi-asserted-by":"publisher","first-page":"619","DOI":"10.1085\/jgp.200910328","article-title":"A malignant hyperthermia-inducing mutation in RYR1 (R163C): alterations inCa2+ entry, release, and retrograde signaling to the DHPR.","volume":"135","author":"Est\u00e8ve","year":"2010","journal-title":"J. Gen. Physiol."},{"key":"B17","doi-asserted-by":"publisher","first-page":"699","DOI":"10.1152\/physrev.1997.77.3.699","article-title":"Ryanodine receptors of striated muscles: acomplex channel capable of multiple interactions.","volume":"77","author":"Franzini-Armstrong","year":"1997","journal-title":"Physiol. Rev."},{"key":"B18","doi-asserted-by":"publisher","DOI":"10.1002\/humu.9442","article-title":"Frequency and localization of mutations in the 106 exons of theRYR1 gene in 50 individuals with malignant hyperthermia.","volume":"27","author":"Galli","year":"2006","journal-title":"Hum. Mutat."},{"key":"B19","doi-asserted-by":"publisher","first-page":"2793","DOI":"10.1021\/bi3015983","article-title":"Effect of calcium on the oxidative phosphorylation cascade in skeletal muscle mitochondria.","volume":"52","author":"Glancy","year":"2013","journal-title":"Biochemistry"},{"key":"B20","doi-asserted-by":"publisher","first-page":"185","DOI":"10.1111\/j.1469-7793.2001.0185b.x","article-title":"Depletion of Ca2+ in the sarcoplasmic reticulum stimulates Ca2+ entry into mouse skeletal muscle fibres.","volume":"533","author":"Kurebayashi","year":"2001","journal-title":"J. Physiol."},{"key":"B21","doi-asserted-by":"publisher","first-page":"244","DOI":"10.1038\/nm.2598","article-title":"AICAR prevents heat-induced sudden death in RyR1 mutant mice independent of AMPK activation.","volume":"18","author":"Lanner","year":"2012","journal-title":"Nat. Med."},{"key":"B22","doi-asserted-by":"publisher","DOI":"10.1016\/j.ccell.2017.03.003","article-title":"Direct pharmacological targeting of a mitochondrial ion channel selectively kills tumor cells in vivo.","volume":"31","author":"Leanza","year":"2017","journal-title":"Cancer Cell."},{"key":"B23","doi-asserted-by":"crossref","first-page":"789","DOI":"10.1126\/science.1589759","article-title":"Malignant hyperthermia.","volume":"256","author":"MacLennan","year":"1992","journal-title":"Science"},{"key":"B24","doi-asserted-by":"publisher","first-page":"1269","DOI":"10.1016\/j.celrep.2015.01.056","article-title":"The mitochondrialcalciumuniportercontrolsskeletal muscle trophism in vivo.","volume":"10","author":"Mammucari","year":"2015","journal-title":"Cell Rep."},{"key":"B25","doi-asserted-by":"publisher","first-page":"4439","DOI":"10.1113\/jphysiol.2013.259572","article-title":"Altered Ca2+ concentration, permeability andbuffering in the myofibre Ca2+ store of a mouse model of malignant hyperthermia.","volume":"591","author":"Manno","year":"2013","journal-title":"J. Physiol."},{"key":"B26","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0201050","article-title":"3Ddiffusional-compartmental model of the calcium dynamics in cytosol, sarcoplasmic reticulum and mitochondria of murine skeletal muscle fibers.","volume":"13","author":"Marcucci","year":"2018","journal-title":"PLoS One"},{"key":"B27","doi-asserted-by":"crossref","first-page":"437","DOI":"10.1213\/00000539-198910000-00003","article-title":"Malignant hyperthermia inhumans\u2013standardization of contracture testing protocol.","volume":"69","author":"Melton","year":"1989","journal-title":"Anesth. Analg."},{"key":"B28","doi-asserted-by":"publisher","first-page":"522","DOI":"10.1002\/mus.21724","article-title":"Mitochondrial redox potential duringcontraction in single intact muscle fibers.","volume":"42","author":"Michaelson","year":"2010","journal-title":"Muscle Nerve"},{"key":"B29","doi-asserted-by":"publisher","first-page":"101","DOI":"10.1016\/j.ceca.2018.10.004","article-title":"Role of STIM1\/ORAI1-mediated store-operated Ca(2+) entry in skeletal muscle physiologyand disease.","volume":"76","author":"Michelucci","year":"2018","journal-title":"Cell Calcium"},{"key":"B30","doi-asserted-by":"publisher","first-page":"3649","DOI":"10.1096\/fj.201601292R","article-title":"Strenuous exercise triggers a life-threatening response in mice susceptible tomalignant hyperthermia.","volume":"31","author":"Michelucci","year":"","journal-title":"FASEB J."},{"key":"B31","doi-asserted-by":"publisher","DOI":"10.1155\/2017\/6792694","article-title":"Antioxidanttreatment reduces formation of structural cores, and improves muscle function inRYR1(Y522S\/WT) mice.","volume":"2017","author":"Michelucci","year":"","journal-title":"Oxid. Med. Cell. Longev."},{"key":"B32","doi-asserted-by":"publisher","first-page":"603","DOI":"10.1097\/ALN.0000000000000748","article-title":"Antioxidants protect calsequestrin-1 knockout mice from halothane- and heat-induced sudden death.","volume":"123","author":"Michelucci","year":"2015","journal-title":"Anesthesiology"},{"key":"B33","doi-asserted-by":"publisher","first-page":"521","DOI":"10.1016\/j.chembiol.2006.03.007","article-title":"Ca2+ indicators based on computationally redesigned calmodulin-peptide pairs.","volume":"13","author":"Palmer","year":"2006","journal-title":"Chem. Biol."},{"key":"B34","doi-asserted-by":"publisher","first-page":"17404","DOI":"10.1073\/pnas.0408030101","article-title":"Bcl-2-mediated alterations in endoplasmicreticulum Ca2+ analyzed with an improved genetically encoded fluorescent sensor.","volume":"101","author":"Palmer","year":"2004","journal-title":"Proc. Natl. Acad. Sci. U.S.A."},{"key":"B35","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0096378","article-title":"Skeletalmuscle contractions induce acute changes in cytosolic superoxide, but slowerresponses in mitochondrial superoxide and cellular hydrogen peroxide.","volume":"9","author":"Pearson","year":"2014","journal-title":"PLoS One"},{"key":"B36","doi-asserted-by":"publisher","first-page":"1243","DOI":"10.1152\/physrev.00031.2007","article-title":"Exercise-induced oxidative stress: cellular mechanisms and impact on muscle force production.","volume":"88","author":"Powers","year":"2008","journal-title":"Physiol. Rev."},{"key":"B37","doi-asserted-by":"publisher","first-page":"1035","DOI":"10.1016\/j.tibs.2016.09.001","article-title":"Calcium at the center of cellsignaling: interplay between endoplasmic reticulum, mitochondria, and lysosomes.","volume":"41","author":"Raffaello","year":"2016","journal-title":"Trends Biochem. Sci."},{"key":"B38","doi-asserted-by":"publisher","first-page":"566","DOI":"10.1038\/nrm3412","article-title":"Mitochondriaassensors andregulators of calcium signalling.","volume":"13","author":"Rizzuto","year":"2012","journal-title":"Nat. Rev. Mol. Cell Biol."},{"key":"B39","doi-asserted-by":"publisher","first-page":"941","DOI":"10.1038\/nprot.2008.56","article-title":"The selective detection of mitochondrialsuperoxide by live cell imaging.","volume":"3","author":"Robinson","year":"2008","journal-title":"Nat. Protoc."},{"key":"B40","doi-asserted-by":"publisher","first-page":"527","DOI":"10.1083\/jcb.200403102","article-title":"In vivo monitoring of Ca(2+)uptake into mitochondria of mouse skeletal muscle during contraction.","volume":"166","author":"Rudolf","year":"2004","journal-title":"J. CellBiol."},{"key":"B41","doi-asserted-by":"publisher","first-page":"463","DOI":"10.1146\/annurev.physiol.56.1.463","article-title":"Control of calcium release in functioning skeletal musclefibers.","volume":"56","author":"Schneider","year":"1994","journal-title":"Annu. Rev. Physiol."},{"key":"B42","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0074919","article-title":"Mitochondrial Ca2+ handling in fast skeletalmusclefibers from wild type and calsequestrin-null mice.","volume":"8","author":"Scorzeto","year":"2013","journal-title":"PLoS One"},{"key":"B43","doi-asserted-by":"publisher","first-page":"13985","DOI":"10.1021\/bi8012627","article-title":"Regulation of the cardiac muscle ryanodine receptor by O(2) tension and S-nitrosoglutathione.","volume":"47","author":"Sun","year":"2008","journal-title":"Biochemistry"},{"key":"B44","doi-asserted-by":"publisher","first-page":"22961","DOI":"10.1074\/jbc.M113.480228","article-title":"Oxygen-coupled redox regulation of the skeletal muscle ryanodine receptor\/Ca2+release channel (RyR1): sites and nature of oxidative modification.","volume":"288","author":"Sun","year":"2013","journal-title":"J. Biol. Chem."},{"key":"B45","doi-asserted-by":"publisher","first-page":"760","DOI":"10.1016\/j.molcel.2016.10.001","article-title":"A MICU1 splicevariantconfers high sensitivity to the mitochondrial Ca(2+) uptake machinery of skeletalmuscle.","volume":"64","author":"Vecellio Reane","year":"2016","journal-title":"Mol. Cell."},{"key":"B46","doi-asserted-by":"publisher","first-page":"3068","DOI":"10.1096\/fj.11-187252","article-title":"Mitochondrial superoxide flashes: metabolic biomarkers of skeletal muscleactivity and disease.","volume":"25","author":"Wei","year":"2011","journal-title":"FASEB J."},{"key":"B47","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0077633","article-title":"Accelerated activation of SOCE current in myotubes from two mouse models of anesthetic- and heat-induced sudden death.","volume":"8","author":"Yarotskyy","year":"2013","journal-title":"PLoS One"},{"key":"B48","doi-asserted-by":"publisher","first-page":"33477","DOI":"10.1074\/jbc.m602306200","article-title":"Azumoleneinhibits a component of store-operated calcium entry coupled to the skeletalmuscle ryanodine receptor.","volume":"281","author":"Zhao","year":"2006","journal-title":"J. Biol. Chem."},{"key":"B49","doi-asserted-by":"publisher","first-page":"111","DOI":"10.1085\/jgp.201711864","article-title":"Voltagemodulates halothane-triggered Ca(2+) release in malignant hyperthermia-susceptible muscle.","volume":"150","author":"Zullo","year":"2018","journal-title":"J. Gen. Physiol."}],"container-title":["Frontiers in Physiology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/article\/10.3389\/fphys.2019.01142\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2019,9,13]],"date-time":"2019-09-13T09:42:19Z","timestamp":1568367739000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/article\/10.3389\/fphys.2019.01142\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2019,9,13]]},"references-count":49,"alternative-id":["10.3389\/fphys.2019.01142"],"URL":"https:\/\/doi.org\/10.3389\/fphys.2019.01142","relation":{},"ISSN":["1664-042X"],"issn-type":[{"value":"1664-042X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2019,9,13]]},"article-number":"1142"}}