{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,14]],"date-time":"2026-10-14T01:21:30Z","timestamp":1791940890898,"version":"4.3.4"},"reference-count":65,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2021,3,25]],"date-time":"2021-03-25T00:00:00Z","timestamp":1616630400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000057","name":"National Institute of General Medical Sciences","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100000057","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Cell Dev. Biol."],"abstract":"<jats:p>\n                    Mammalian mitochondria are emerging as a critical stress-responsive contributor to cellular life\/death and developmental outcomes. Maintained as an organellar network distributed throughout the cell, mitochondria respond to cellular stimuli and stresses through highly sensitive structural dynamics, particularly in energetically demanding cell settings such as cardiac and muscle tissues. Fusion allows individual mitochondria to form an interconnected reticular network, while fission divides the network into a collection of vesicular organelles. Crucially,\n                    <jats:underline>op<\/jats:underline>\n                    tic\n                    <jats:underline>a<\/jats:underline>\n                    trophy-\n                    <jats:underline>1<\/jats:underline>\n                    (OPA1) directly links mitochondrial structure and bioenergetic function: when the transmembrane potential across the inner membrane (\u0394\u03a8\n                    <jats:sub>m<\/jats:sub>\n                    ) is intact, long L-OPA1 isoforms carry out fusion of the mitochondrial inner membrane. When \u0394\u03a8\n                    <jats:sub>m<\/jats:sub>\n                    is lost, L-OPA1 is cleaved to short, fusion-inactive S-OPA1 isoforms by the stress-sensitive OMA1 metalloprotease, causing the mitochondrial network to collapse to a fragmented population of organelles. This proteolytic mechanism provides sensitive regulation of organellar structure\/function but also engages directly with apoptotic factors as a major mechanism of mitochondrial participation in cellular stress response. Furthermore, emerging evidence suggests that this proteolytic mechanism may have critical importance for cell developmental programs, particularly in cardiac, neuronal, and stem cell settings. OMA1\u2019s role as a key mitochondrial stress-sensitive protease motivates exciting new questions regarding its mechanistic regulation and interactions, as well as its broader importance through involvement in apoptotic, stress response, and developmental pathways.\n                  <\/jats:p>","DOI":"10.3389\/fcell.2021.626117","type":"journal-article","created":{"date-parts":[[2021,3,25]],"date-time":"2021-03-25T01:47:22Z","timestamp":1616636842000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":142,"title":["Mitochondrial OMA1 and OPA1 as Gatekeepers of Organellar Structure\/Function and Cellular Stress Response"],"prefix":"10.3389","volume":"9","author":[{"given":"Robert","family":"Gilkerson","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Patrick","family":"De La Torre","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shaynah","family":"St. Vallier","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2021,3,25]]},"reference":[{"key":"B1","doi-asserted-by":"crossref","DOI":"10.1083\/jcb.201911122","article-title":"Fission and fusion machineries converge at ER contact sites to regulate mitochondrial morphology.","volume":"219","author":"Abrisch","year":"2020","journal-title":"J. Cell Biol."},{"key":"B2","doi-asserted-by":"crossref","DOI":"10.1126\/scitranslmed.aan4935","article-title":"Ablation of the stress protease OMA1 protects against heart failure in mice.","volume":"10","author":"Acin-Perez","year":"2018","journal-title":"Sci. Transl. Med."},{"key":"B3","doi-asserted-by":"publisher","first-page":"481","DOI":"10.1083\/jcb.107.2.481","article-title":"Coupling membranes as energy-transmitting cables. I. filamentous mitochondria in fibroblasts and mitochondrial clusters in cardiomyocytes.","volume":"107","author":"Amchenkova","year":"1988","journal-title":"J. Cell Biol."},{"key":"B4","doi-asserted-by":"publisher","first-page":"919","DOI":"10.1083\/jcb.201308006","article-title":"The i-AAA protease YME1L and OMA1 cleave OPA1 to balance mitochondrial fusion and fission.","volume":"204","author":"Anand","year":"2014","journal-title":"J. Cell Biol."},{"key":"B5","doi-asserted-by":"publisher","first-page":"1896","DOI":"10.1038\/s41418-019-0469-4","article-title":"Prohibitin levels regulate OMA1 activity and turnover in neurons.","volume":"27","author":"Anderson","year":"2019","journal-title":"Cell Death Differ."},{"key":"B6","doi-asserted-by":"publisher","first-page":"578","DOI":"10.1002\/embj.201386474","article-title":"Stress-induced OMA1 activation and autocatalytic turnover regulate OPA1-dependent mitochondrial dynamics.","volume":"33","author":"Baker","year":"2014","journal-title":"EMBO J."},{"key":"B7","doi-asserted-by":"publisher","first-page":"856","DOI":"10.1038\/ncb3560","article-title":"Molecular basis of selective mitochondrial fusion by heterotypic action between OPA1 and cardiolipin.","volume":"19","author":"Ban","year":"2017","journal-title":"Nat. Cell Biol."},{"key":"B8","doi-asserted-by":"publisher","first-page":"37","DOI":"10.1093\/emboj\/17.1.37","article-title":"Mitochondrial cytochrome c release in apoptosis occurs upstream of DEVD-specific caspase activation and independently of mitochondrial transmembrane depolarization.","volume":"17","author":"Bossy-Wetzel","year":"1998","journal-title":"EMBO J."},{"key":"B9","doi-asserted-by":"publisher","DOI":"10.1016\/j.isci.2020.101154","article-title":"Optic Atrophy 1 Controls Human Neuronal Development by Preventing Aberrant Nuclear DNA Methylation.","volume":"23","author":"Caglayan","year":"2020","journal-title":"iScience"},{"key":"B10","doi-asserted-by":"publisher","first-page":"189","DOI":"10.1083\/jcb.200211046","article-title":"Mitofusins Mfn1 and Mfn2 coordinately regulate mitochondrial fusion and are essential for embryonic development.","volume":"160","author":"Chen","year":"2003","journal-title":"J. Cell Biol."},{"key":"B11","doi-asserted-by":"publisher","first-page":"163","DOI":"10.1016\/j.cell.2006.06.021","article-title":"Mitochondrial rhomboid PARL regulates cytochrome c release during apoptosis via OPA1-dependent cristae remodeling.","volume":"126","author":"Cipolat","year":"2006","journal-title":"Cell"},{"key":"B12","doi-asserted-by":"crossref","DOI":"10.1038\/s41598-019-49327-2","article-title":"Depletion of mitochondrial protease OMA1 alters proliferative properties and promotes metastatic growth of breast cancer cells.","volume":"9","author":"Daverey","year":"2019","journal-title":"Sci. Rep."},{"key":"B13","doi-asserted-by":"publisher","first-page":"15716","DOI":"10.1523\/jneurosci.3159-11.2011","article-title":"PKA\/AKAP1 and PP2A\/Bbeta2 regulate neuronal morphogenesis via Drp1 phosphorylation and mitochondrial bioenergetics.","volume":"31","author":"Dickey","year":"2011","journal-title":"J. Neurosci."},{"key":"B14","doi-asserted-by":"crossref","first-page":"2656","DOI":"10.1056\/NEJMra022567","article-title":"Mitochondrial respiratory-chain diseases.","volume":"348","author":"DiMauro","year":"2003","journal-title":"N. Engl. J. Med."},{"key":"B15","doi-asserted-by":"publisher","first-page":"1023","DOI":"10.1083\/jcb.200906084","article-title":"Regulation of OPA1 processing and mitochondrial fusion by m-AAA protease isoenzymes and OMA1.","volume":"187","author":"Ehses","year":"2009","journal-title":"J. Cell Biol."},{"key":"B16","doi-asserted-by":"crossref","first-page":"227s","DOI":"10.1083\/jcb.91.3.227s","article-title":"Mitochondria: a historical review.","volume":"91","author":"Ernster","year":"1981","journal-title":"J. Cell Biol."},{"key":"B17","doi-asserted-by":"publisher","first-page":"429","DOI":"10.1038\/s41586-019-1372-3","article-title":"Structure and assembly of the mitochondrial membrane remodelling GTPase Mgm1.","volume":"571","author":"Faelber","year":"2019","journal-title":"Nature"},{"key":"B18","doi-asserted-by":"publisher","first-page":"433","DOI":"10.1038\/s41586-020-2076-4","article-title":"A pathway coordinated by DELE1 relays mitochondrial stress to the cytosol.","volume":"579","author":"Fessler","year":"2020","journal-title":"Nature"},{"key":"B19","doi-asserted-by":"crossref","first-page":"E34","DOI":"10.1038\/s41586-019-1296-y","article-title":"Mitochondrial fission requires DRP1 but not dynamins.","volume":"570","author":"Fonseca","year":"2019","journal-title":"Nature"},{"key":"B20","doi-asserted-by":"publisher","first-page":"319","DOI":"10.1016\/s0968-0004(00)01609-1","article-title":"The internal structure of mitochondria.","volume":"25","author":"Frey","year":"2000","journal-title":"Trends Biochem. Sci."},{"key":"B21","doi-asserted-by":"publisher","first-page":"177","DOI":"10.1016\/j.cell.2006.06.025","article-title":"OPA1 controls apoptotic cristae remodeling independently from mitochondrial fusion.","volume":"126","author":"Frezza","year":"2006","journal-title":"Cell"},{"key":"B22","doi-asserted-by":"publisher","first-page":"358","DOI":"10.1126\/science.1207385","article-title":"ER tubules mark sites of mitochondrial division.","volume":"334","author":"Friedman","year":"2011","journal-title":"Science"},{"key":"B23","doi-asserted-by":"publisher","first-page":"2402","DOI":"10.1091\/mbc.e07-12-1287","article-title":"The novel tail-anchored membrane protein Mff controls mitochondrial and peroxisomal fission in mammalian cells.","volume":"19","author":"Gandre-Babbe","year":"2008","journal-title":"Mol. Biol. Cell"},{"key":"B24","doi-asserted-by":"publisher","first-page":"160","DOI":"10.1080\/13510002.2018.1492766","article-title":"Oxidative insults disrupt OPA1-mediated mitochondrial dynamics in cultured mammalian cells.","volume":"23","author":"Garcia","year":"2018","journal-title":"Redox. Rep."},{"key":"B25","doi-asserted-by":"publisher","first-page":"757","DOI":"10.1083\/jcb.200704112","article-title":"Regulation of the mitochondrial dynamin-like protein Opa1 by proteolytic cleavage.","volume":"178","author":"Griparic","year":"2007","journal-title":"J. Cell Biol."},{"key":"B26","doi-asserted-by":"publisher","first-page":"18792","DOI":"10.1074\/jbc.m400920200","article-title":"Loss of the intermembrane space protein Mgm1\/OPA1 induces swelling and localized constrictions along the lengths of mitochondria.","volume":"279","author":"Griparic","year":"2004","journal-title":"J. Biol. Chem."},{"key":"B27","doi-asserted-by":"publisher","first-page":"315","DOI":"10.1042\/bc20070110","article-title":"Metalloprotease-mediated OPA1 processing is modulated by the mitochondrial membrane potential.","volume":"100","author":"Guillery","year":"2008","journal-title":"Biol. Cell"},{"key":"B28","doi-asserted-by":"publisher","first-page":"427","DOI":"10.1038\/s41586-020-2078-2","article-title":"Mitochondrial stress is relayed to the cytosol by an OMA1-DELE1-HRI pathway.","volume":"579","author":"Guo","year":"2020","journal-title":"Nature"},{"key":"B29","doi-asserted-by":"publisher","first-page":"959","DOI":"10.1083\/jcb.200906083","article-title":"Inducible proteolytic inactivation of OPA1 mediated by the OMA1 protease in mammalian cells.","volume":"187","author":"Head","year":"2009","journal-title":"J. Cell Biol."},{"key":"B30","doi-asserted-by":"crossref","DOI":"10.1038\/s41419-020-03152-y","article-title":"OPA1 and MICOS Regulate mitochondrial crista dynamics and formation.","volume":"11","author":"Hu","year":"2020","journal-title":"Cell Death Dis."},{"key":"B31","doi-asserted-by":"publisher","first-page":"2966","DOI":"10.1038\/sj.emboj.7601184","article-title":"Regulation of mitochondrial morphology through proteolytic cleavage of OPA1.","volume":"25","author":"Ishihara","year":"2006","journal-title":"EMBO J."},{"key":"B32","doi-asserted-by":"crossref","DOI":"10.7554\/eLife.11553","article-title":"Actin filaments target the oligomeric maturation of the dynamin GTPase Drp1 to mitochondrial fission sites.","volume":"4","author":"Ji","year":"2015","journal-title":"Elife"},{"key":"B33","doi-asserted-by":"publisher","first-page":"14782","DOI":"10.1073\/pnas.1417253111","article-title":"Activation of mitochondrial protease OMA1 by Bax and Bak promotes cytochrome c release during apoptosis.","volume":"111","author":"Jiang","year":"2014","journal-title":"Proc. Natl. Acad. Sci. U. S. A."},{"key":"B34","doi-asserted-by":"publisher","first-page":"915","DOI":"10.1002\/ana.25221","article-title":"Stem cell modeling of mitochondrial parkinsonism reveals key functions of OPA1.","volume":"83","author":"Jonikas","year":"2018","journal-title":"Ann. Neurol."},{"key":"B35","doi-asserted-by":"publisher","first-page":"734","DOI":"10.1126\/science.1241359","article-title":"Mitochondrial fusion directs cardiomyocyte differentiation via calcineurin and Notch signaling.","volume":"342","author":"Kasahara","year":"2013","journal-title":"Science"},{"key":"B36","doi-asserted-by":"publisher","first-page":"46414","DOI":"10.1074\/jbc.m305584200","article-title":"Oma1, a novel membrane-bound metallopeptidase in mitochondria with activities overlapping with the m-AAA protease.","volume":"278","author":"Kaser","year":"2003","journal-title":"J. Biol. Chem."},{"key":"B37","doi-asserted-by":"publisher","first-page":"157","DOI":"10.1083\/jcb.201507022","article-title":"Loss of OMA1 delays neurodegeneration by preventing stress-induced OPA1 processing in mitochondria.","volume":"212","author":"Korwitz","year":"2016","journal-title":"J. Cell Biol."},{"key":"B38","doi-asserted-by":"publisher","first-page":"2163","DOI":"10.18632\/aging.101307","article-title":"SIRT4 interacts with OPA1 and regulates mitochondrial quality control and mitophagy.","volume":"9","author":"Lang","year":"2017","journal-title":"Aging"},{"key":"B39","doi-asserted-by":"publisher","first-page":"6543","DOI":"10.1074\/jbc.ra119.010983","article-title":"The short variant of optic atrophy 1 (OPA1) improves cell survival under oxidative stress.","volume":"295","author":"Lee","year":"2020","journal-title":"J. Biol. Chem."},{"key":"B40","doi-asserted-by":"publisher","first-page":"7115","DOI":"10.1074\/jbc.m116.762567","article-title":"The short variant of the mitochondrial dynamin OPA1 maintains mitochondrial energetics and cristae structure.","volume":"292","author":"Lee","year":"2017","journal-title":"J. Biol. Chem."},{"key":"B41","doi-asserted-by":"publisher","first-page":"139","DOI":"10.1038\/nature20555","article-title":"Multiple dynamin family members collaborate to drive mitochondrial division.","volume":"540","author":"Lee","year":"2016","journal-title":"Nature"},{"key":"B42","doi-asserted-by":"publisher","first-page":"4737","DOI":"10.1021\/acs.biochem.7b00663","article-title":"Metalloproteases of the Inner Mitochondrial Membrane.","volume":"56","author":"Levytskyy","year":"2017","journal-title":"Biochemistry"},{"key":"B43","doi-asserted-by":"publisher","first-page":"659","DOI":"10.1091\/mbc.e12-10-0721","article-title":"Fis1, Mff, MiD49, and MiD51 mediate Drp1 recruitment in mitochondrial fission.","volume":"24","author":"Loson","year":"2013","journal-title":"Mol. Biol. Cell"},{"key":"B44","doi-asserted-by":"publisher","DOI":"10.3389\/fnins.2020.571479","article-title":"Optimized OPA1 Isoforms 1 and 7 Provide Therapeutic Benefit in Models of Mitochondrial Dysfunction.","volume":"14","author":"Maloney","year":"2020","journal-title":"Front. Neurosci."},{"key":"B45","doi-asserted-by":"crossref","DOI":"10.15252\/embj.2020105074","article-title":"Mitochondrial Safeguard: a stress response that offsets extreme fusion and protects respiratory function via flickering-induced Oma1 activation.","volume":"39","author":"Murata","year":"2020","journal-title":"EMBO J."},{"key":"B46","doi-asserted-by":"crossref","DOI":"10.1038\/s41598-020-67457-w","article-title":"p32\/C1QBP regulates OMA1-dependent proteolytic processing of OPA1 to maintain mitochondrial connectivity related to mitochondrial dysfunction and apoptosis.","volume":"10","author":"Noh","year":"2020","journal-title":"Sci. Rep."},{"key":"B47","doi-asserted-by":"publisher","first-page":"171","DOI":"10.1016\/s0014-5793(02)02985-x","article-title":"The human dynamin-related protein OPA1 is anchored to the mitochondrial inner membrane facing the inter-membrane space.","volume":"523","author":"Olichon","year":"2002","journal-title":"FEBS Lett."},{"key":"B48","doi-asserted-by":"publisher","first-page":"427","DOI":"10.1002\/ar.1091140304","article-title":"The fine structure of mitochondria.","volume":"114","author":"Palade","year":"1952","journal-title":"Anat. Rec."},{"key":"B49","doi-asserted-by":"publisher","first-page":"27584","DOI":"10.1074\/jbc.m113.479873","article-title":"Adaptor proteins MiD49 and MiD51 can act independently of Mff and Fis1 in Drp1 recruitment and are specific for mitochondrial fission.","volume":"288","author":"Palmer","year":"2013","journal-title":"J. Biol. Chem."},{"key":"B50","doi-asserted-by":"publisher","first-page":"2676","DOI":"10.15252\/embj.201488349","article-title":"OPA1-dependent cristae modulation is essential for cellular adaptation to metabolic demand.","volume":"33","author":"Patten","year":"2014","journal-title":"EMBO J."},{"key":"B51","doi-asserted-by":"publisher","first-page":"2041","DOI":"10.1016\/j.celrep.2016.02.011","article-title":"Reciprocal Degradation of YME1L and OMA1 Adapts Mitochondrial Proteolytic Activity during Stress.","volume":"14","author":"Rainbolt","year":"2016","journal-title":"Cell Rep."},{"key":"B52","doi-asserted-by":"publisher","first-page":"97","DOI":"10.15252\/embr.201438976","article-title":"YME1L degradation reduces mitochondrial proteolytic capacity during oxidative stress.","volume":"16","author":"Rainbolt","year":"2015","journal-title":"EMBO Rep."},{"key":"B53","doi-asserted-by":"publisher","first-page":"1763","DOI":"10.1126\/science.280.5370.1763","article-title":"Close contacts with the endoplasmic reticulum as determinants of mitochondrial Ca2+ responses.","volume":"280","author":"Rizzuto","year":"1998","journal-title":"Science"},{"key":"B54","doi-asserted-by":"crossref","first-page":"867","DOI":"10.1242\/jcs.114.5.867","article-title":"Control of mitochondrial morphology by a human mitofusin.","volume":"114","author":"Santel","year":"2001","journal-title":"J. Cell Sci."},{"key":"B55","doi-asserted-by":"publisher","first-page":"30","DOI":"10.1038\/171030a0","article-title":"Electron microscopy of mitochondria and cytoplasmic double membranes.","volume":"171","author":"Sjostrand","year":"1953","journal-title":"Nature"},{"key":"B56","doi-asserted-by":"publisher","first-page":"909","DOI":"10.1038\/sj.cdd.4400889","article-title":"Bax translocation to mitochondria subsequent to a rapid loss of mitochondrial membrane potential.","volume":"8","author":"Smaili","year":"2001","journal-title":"Cell Death Differ."},{"key":"B57","doi-asserted-by":"publisher","first-page":"2245","DOI":"10.1091\/mbc.12.8.2245","article-title":"Dynamin-related protein Drp1 is required for mitochondrial division in mammalian cells.","volume":"12","author":"Smirnova","year":"2001","journal-title":"Mol. Biol. Cell"},{"key":"B58","doi-asserted-by":"crossref","DOI":"10.15252\/embj.2019104105","article-title":"MICOS assembly controls mitochondrial inner membrane remodeling and crista junction redistribution to mediate cristae formation.","volume":"39","author":"Stephan","year":"2020","journal-title":"EMBO J."},{"key":"B59","doi-asserted-by":"crossref","first-page":"1374","DOI":"10.1016\/j.cmet.2017.04.021","article-title":"Age-Associated Loss of OPA1 in Muscle Impacts Muscle Mass, Metabolic Homeostasis, Systemic Inflammation, and Epithelial Senescence.","volume":"25","author":"Tezze","year":"2017","journal-title":"Cell Metab."},{"key":"B60","doi-asserted-by":"publisher","DOI":"10.1126\/science.aad0116","article-title":"Imbalanced OPA1 processing and mitochondrial fragmentation cause heart failure in mice.","volume":"350","author":"Wai","year":"2015","journal-title":"Science"},{"key":"B61","doi-asserted-by":"publisher","first-page":"157","DOI":"10.1091\/mbc.e20-09-0605","article-title":"Identification of new OPA1 cleavage site reveals that short isoforms regulate mitochondrial fusion.","volume":"32","author":"Wang","year":"2020","journal-title":"Mol. Biol. Cell"},{"key":"B62","doi-asserted-by":"publisher","first-page":"557","DOI":"10.1016\/j.molcel.2008.07.010","article-title":"Opa1-mediated cristae opening is Bax\/Bak and BH3 dependent, required for apoptosis, and independent of Bak oligomerization.","volume":"31","author":"Yamaguchi","year":"2008","journal-title":"Mol. Cell"},{"key":"B63","doi-asserted-by":"publisher","first-page":"4061","DOI":"10.1073\/pnas.1919116117","article-title":"Structural analysis of a trimeric assembly of the mitochondrial dynamin-like GTPase Mgm1.","volume":"117","author":"Yan","year":"2020","journal-title":"Proc. Natl. Acad. Sci. U. S. A."},{"key":"B64","doi-asserted-by":"crossref","DOI":"10.15252\/embj.201899748","article-title":"Human Fis1 regulates mitochondrial dynamics through inhibition of the fusion machinery.","volume":"38","author":"Yu","year":"2019","journal-title":"EMBO J."},{"key":"B65","doi-asserted-by":"publisher","first-page":"576","DOI":"10.1002\/embr.201338240","article-title":"Membrane depolarization activates the mitochondrial protease OMA1 by stimulating self-cleavage.","volume":"15","author":"Zhang","year":"2014","journal-title":"EMBO Rep."}],"container-title":["Frontiers in Cell and Developmental Biology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fcell.2021.626117\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2021,4,30]],"date-time":"2021-04-30T00:41:04Z","timestamp":1619743264000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fcell.2021.626117\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,3,25]]},"references-count":65,"alternative-id":["10.3389\/fcell.2021.626117"],"URL":"https:\/\/doi.org\/10.3389\/fcell.2021.626117","relation":{},"ISSN":["2296-634X"],"issn-type":[{"value":"2296-634X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,3,25]]},"article-number":"626117"}}