{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,5]],"date-time":"2026-10-05T14:29:03Z","timestamp":1791210543945,"version":"4.1.0"},"reference-count":31,"publisher":"Springer Science and Business Media LLC","issue":"7423","license":[{"start":{"date-parts":[[2012,10,10]],"date-time":"2012-10-10T00:00:00Z","timestamp":1349827200000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/www.springer.com\/tdm"},{"start":{"date-parts":[[2012,10,10]],"date-time":"2012-10-10T00:00:00Z","timestamp":1349827200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/www.springer.com\/tdm"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Nature"],"published-print":{"date-parts":[[2012,11,8]]},"DOI":"10.1038\/nature11444","type":"journal-article","created":{"date-parts":[[2012,10,9]],"date-time":"2012-10-09T12:31:36Z","timestamp":1349785896000},"page":"269-273","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":390,"title":["CaMKII determines mitochondrial stress responses in heart"],"prefix":"10.1038","volume":"491","author":[{"given":"Mei-ling A.","family":"Joiner","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Olha M.","family":"Koval","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jingdong","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"B. Julie","family":"He","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chantal","family":"Allamargot","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhan","family":"Gao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elizabeth D.","family":"Luczak","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Duane D.","family":"Hall","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Brian D.","family":"Fink","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Biyi","family":"Chen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jinying","family":"Yang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Steven A.","family":"Moore","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thomas D.","family":"Scholz","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stefan","family":"Strack","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peter J.","family":"Mohler","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"William I.","family":"Sivitz","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Long-Sheng","family":"Song","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mark E.","family":"Anderson","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2012,10,10]]},"reference":[{"key":"BFnature11444_CR1","doi-asserted-by":"publisher","first-page":"513","DOI":"10.1038\/74994","volume":"6","author":"G Kroemer","year":"2000","unstructured":"Kroemer, G. & Reed, J. C. Mitochondrial control of cell death. Nature Med. 6, 513\u2013519 (2000)","journal-title":"Nature Med."},{"key":"BFnature11444_CR2","doi-asserted-by":"publisher","first-page":"1047","DOI":"10.1016\/j.cell.2007.11.028","volume":"131","author":"DE Clapham","year":"2007","unstructured":"Clapham, D. E. Calcium signaling. Cell 131, 1047\u20131058 (2007)","journal-title":"Cell"},{"key":"BFnature11444_CR3","doi-asserted-by":"publisher","first-page":"360","DOI":"10.1038\/nature02246","volume":"427","author":"Y Kirichok","year":"2004","unstructured":"Kirichok, Y., Krapivinsky, G. & Clapham, D. E. The mitochondrial calcium uniporter is a highly selective ion channel. Nature 427, 360\u2013364 (2004)","journal-title":"Nature"},{"key":"BFnature11444_CR4","doi-asserted-by":"publisher","first-page":"341","DOI":"10.1038\/nature10234","volume":"476","author":"JM Baughman","year":"2011","unstructured":"Baughman, J. M. et al. Integrative genomics identifies MCU as an essential component of the mitochondrial calcium uniporter. Nature 476, 341\u2013345 (2011)","journal-title":"Nature"},{"key":"BFnature11444_CR5","doi-asserted-by":"publisher","first-page":"336","DOI":"10.1038\/nature10230","volume":"476","author":"D De Stefani","year":"2011","unstructured":"De Stefani, D., Raffaello, A., Teardo, E., Szabo, I. & Rizzuto, R. A forty-kilodalton protein of the inner membrane is the mitochondrial calcium uniporter. Nature 476, 336\u2013340 (2011)","journal-title":"Nature"},{"key":"BFnature11444_CR6","doi-asserted-by":"publisher","first-page":"473","DOI":"10.1056\/NEJMoa071142","volume":"359","author":"C Piot","year":"2008","unstructured":"Piot, C. et al. Effect of cyclosporine on reperfusion injury in acute myocardial infarction. N. Engl. J. Med. 359, 473\u2013481 (2008)","journal-title":"N. Engl. J. Med."},{"key":"BFnature11444_CR7","doi-asserted-by":"publisher","first-page":"462","DOI":"10.1016\/j.cell.2008.02.048","volume":"133","author":"JR Erickson","year":"2008","unstructured":"Erickson, J. R. et al. A dynamic pathway for calcium-independent activation of CaMKII by methionine oxidation. Cell 133, 462\u201374 (2008)","journal-title":"Cell"},{"key":"BFnature11444_CR8","doi-asserted-by":"publisher","first-page":"H3065","DOI":"10.1152\/ajpheart.00353.2006","volume":"291","author":"Y Yang","year":"2006","unstructured":"Yang, Y. et al. Calmodulin kinase II inhibition protects against myocardial cell apoptosis in vivo. Am. J. Physiol. Heart Circ. Physiol. 291, H3065\u2013H3075 (2006)","journal-title":"Am. J. Physiol. Heart Circ. Physiol."},{"key":"BFnature11444_CR9","doi-asserted-by":"publisher","first-page":"912","DOI":"10.1161\/01.RES.0000069686.31472.C5","volume":"92","author":"T Zhang","year":"2003","unstructured":"Zhang, T. et al. The \u03b4C isoform of CaMKII is activated in cardiac hypertrophy and induces dilated cardiomyopathy and heart failure. Circ. Res. 92, 912\u2013919 (2003)","journal-title":"Circ. Res."},{"key":"BFnature11444_CR10","doi-asserted-by":"publisher","first-page":"989","DOI":"10.1016\/j.yjmcc.2008.12.022","volume":"46","author":"K Odagiri","year":"2009","unstructured":"Odagiri, K. et al. Local control of mitochondrial membrane potential, permeability transition pore and reactive oxygen species by calcium and calmodulin in rat ventricular myocytes. J. Mol. Cell. Cardiol. 46, 989\u2013997 (2009)","journal-title":"J. Mol. Cell. Cardiol."},{"key":"BFnature11444_CR11","doi-asserted-by":"publisher","first-page":"409","DOI":"10.1038\/nm1215","volume":"11","author":"R Zhang","year":"2005","unstructured":"Zhang, R. et al. Calmodulin kinase II inhibition protects against structural heart disease. Nature Med. 11, 409\u2013417 (2005)","journal-title":"Nature Med."},{"key":"BFnature11444_CR12","doi-asserted-by":"publisher","first-page":"829","DOI":"10.1038\/sj.bjp.0706932","volume":"149","author":"GJ Garc\u00eda-Rivas","year":"2006","unstructured":"Garc\u00eda-Rivas, G. J., Carvajal, K., Correa, F. & Zazueta, C. Ru360, a specific mitochondrial calcium uptake inhibitor, improves cardiac post-ischaemic functional recovery in rats in vivo. Br. J. Pharmacol. 149, 829\u2013837 (2006)","journal-title":"Br. J. Pharmacol."},{"key":"BFnature11444_CR13","doi-asserted-by":"publisher","first-page":"986","DOI":"10.1172\/JCI35541","volume":"119","author":"MV Singh","year":"2009","unstructured":"Singh, M. V. et al. Ca2+\/calmodulin-dependent kinase II triggers cell membrane injury by inducing complement factor B gene expression in the mouse heart. J. Clin. Invest. 119, 986\u2013996 (2009)","journal-title":"J. Clin. Invest."},{"key":"BFnature11444_CR14","doi-asserted-by":"publisher","first-page":"339","DOI":"10.1016\/S0092-8674(00)81477-4","volume":"94","author":"R Hakem","year":"1998","unstructured":"Hakem, R. et al. Differential requirement for Caspase 9 in apoptotic pathways in vivo. Cell 94, 339\u2013352 (1998)","journal-title":"Cell"},{"key":"BFnature11444_CR15","doi-asserted-by":"publisher","first-page":"7743","DOI":"10.1074\/jbc.C200677200","volume":"278","author":"A Olichon","year":"2003","unstructured":"Olichon, A. et al. Loss of OPA1 perturbates the mitochondrial inner membrane structure and integrity, leading to cytochrome c release and apoptosis. J. Biol. Chem. 278, 7743\u20137746 (2003)","journal-title":"J. Biol. Chem."},{"key":"BFnature11444_CR16","doi-asserted-by":"publisher","first-page":"279","DOI":"10.1016\/j.cell.2008.06.017","volume":"134","author":"W Wang","year":"2008","unstructured":"Wang, W. et al. Superoxide flashes in single mitochondria. Cell 134, 279\u2013290 (2008)","journal-title":"Cell"},{"key":"BFnature11444_CR17","doi-asserted-by":"publisher","first-page":"821","DOI":"10.1016\/j.yjmcc.2009.02.021","volume":"46","author":"AP Halestrap","year":"2009","unstructured":"Halestrap, A. P. What is the mitochondrial permeability transition pore? J. Mol. Cell. Cardiol. 46, 821\u2013831 (2009)","journal-title":"J. Mol. Cell. Cardiol."},{"key":"BFnature11444_CR18","doi-asserted-by":"publisher","first-page":"2925","DOI":"10.1172\/JCI38857","volume":"119","author":"JM Timmins","year":"2009","unstructured":"Timmins, J. M. et al. Calcium\/calmodulin-dependent protein kinase II links ER stress with Fas and mitochondrial apoptosis pathways. J. Clin. Invest. 119, 2925\u20132941 (2009)","journal-title":"J. Clin. Invest."},{"key":"BFnature11444_CR19","doi-asserted-by":"publisher","first-page":"223","DOI":"10.1007\/s11010-009-0303-2","volume":"337","author":"V Sharma","year":"2010","unstructured":"Sharma, V., Abraham, T., So, A., Allard, M. & McNeill, J. Functional effects of protein kinases and peroxynitrite on cardiac carnitine palmitoyltransferase-1 in isolated mitochondria. Mol. Cell. Biochem. 337, 223\u2013237 (2010)","journal-title":"Mol. Cell. Biochem."},{"key":"BFnature11444_CR20","doi-asserted-by":"publisher","first-page":"468","DOI":"10.1016\/j.yjmcc.2011.01.012","volume":"51","author":"ME Anderson","year":"2011","unstructured":"Anderson, M. E., Brown, J. H. & Bers, D. M. CaMKII in myocardial hypertrophy and heart failure. J. Mol. Cell. Cardiol. 51, 468\u2013473 (2011)","journal-title":"J. Mol. Cell. Cardiol."},{"key":"BFnature11444_CR21","doi-asserted-by":"publisher","first-page":"882","DOI":"10.1038\/42264","volume":"388","author":"A Miyawaki","year":"1997","unstructured":"Miyawaki, A. et al. Fluorescent indicators for Ca2+ based on green fluorescent proteins and calmodulin. Nature 388, 882\u2013887 (1997)","journal-title":"Nature"},{"key":"BFnature11444_CR22","doi-asserted-by":"publisher","first-page":"H1820","DOI":"10.1152\/ajpheart.00589.2004","volume":"288","author":"M Saotome","year":"2005","unstructured":"Saotome, M. et al. Mitochondrial membrane potential modulates regulation of mitochondrial Ca2+ in rat ventricular myocytes. Am. J. Physiol. Heart Circ. Physiol. 288, H1820\u2013H1828 (2005)","journal-title":"Am. J. Physiol. Heart Circ. Physiol."},{"key":"BFnature11444_CR23","doi-asserted-by":"crossref","first-page":"16759","DOI":"10.1016\/S0021-9258(19)84770-1","volume":"264","author":"YL Fong","year":"1989","unstructured":"Fong, Y. L., Taylor, W. L., Means, A. R. & Soderling, T. R. Studies of the regulatory mechanism of Ca2+\/calmodulin-dependent protein kinase II. Mutation of threonine 286 to alanine and aspartate. J. Biol. Chem. 264, 16759\u201316763 (1989)","journal-title":"J. Biol. Chem."},{"key":"BFnature11444_CR24","doi-asserted-by":"publisher","first-page":"943","DOI":"10.1016\/0896-6273(94)90306-9","volume":"12","author":"PI Hanson","year":"1994","unstructured":"Hanson, P. I., Meyer, T., Stryer, L. & Schulman, H. Dual role of calmodulin in autophosphorylation of multifunctional cam kinase may underlie decoding of calcium signals. Neuron 12, 943\u2013956 (1994)","journal-title":"Neuron"},{"key":"BFnature11444_CR25","doi-asserted-by":"publisher","first-page":"4996","DOI":"10.1073\/pnas.0913760107","volume":"107","author":"OM Koval","year":"2010","unstructured":"Koval, O. M. et al. CaV1.2 b-subunit coordinates CaMKII-triggered cardiomyocyte death and afterdepolarizations. Proc. Natl Acad. Sci. USA 107, 4996\u20135000 (2010)","journal-title":"Proc. Natl Acad. Sci. USA"},{"key":"BFnature11444_CR26","doi-asserted-by":"publisher","first-page":"e61","DOI":"10.1161\/01.RES.0000125626.33738.E2","volume":"94","author":"XHT Wehrens","year":"2004","unstructured":"Wehrens, X. H. T., Lehnart, S. E., Reiken, S. R. & Marks, A. R. Ca2+\/calmodulin-dependent protein kinase II phosphorylation regulates the cardiac ryanodine receptor. Circ. Res. 94, e61\u2013e70 (2004)","journal-title":"Circ. Res."},{"key":"BFnature11444_CR27","doi-asserted-by":"publisher","first-page":"475","DOI":"10.1038\/ncpcardio0309","volume":"2","author":"DS Feldman","year":"2005","unstructured":"Feldman, D. S., Carnes, C. A., Abraham, W. T. & Bristow, M. R. Mechanisms of disease: \u03b2-adrenergic receptors\u2014alterations in signal transduction and pharmacogenomics in heart failure. Nature Clin. Pract. Cardiovasc. Med. 2, 475\u2013483 (2005)","journal-title":"Nature Clin. Pract. Cardiovasc. Med."},{"key":"BFnature11444_CR28","doi-asserted-by":"publisher","first-page":"2877","DOI":"10.1073\/pnas.051449198","volume":"98","author":"Y Wu","year":"2001","unstructured":"Wu, Y., Colbran, R. J. & Anderson, M. E. Calmodulin kinase is a molecular switch for cardiac excitation-contraction coupling. Proc. Natl Acad. Sci. USA 98, 2877\u20132881 (2001)","journal-title":"Proc. Natl Acad. Sci. USA"},{"key":"BFnature11444_CR29","doi-asserted-by":"publisher","first-page":"387","DOI":"10.4161\/chan.5449","volume":"1","author":"J Li","year":"2007","unstructured":"Li, J. et al. Calmodulin kinase II inhibition enhances ischemic preconditioning by augmenting ATP-sensitive K+ current. Channels 1, 387\u2013394 (2007)","journal-title":"Channels"},{"key":"BFnature11444_CR30","doi-asserted-by":"publisher","first-page":"1610","DOI":"10.1038\/nm.2506","volume":"17","author":"BJ He","year":"2011","unstructured":"He, B. J. et al. Oxidation of CaMKII determines the cardiotoxic effects of aldosterone. Nature Med. 17, 1610\u20131618 (2011)","journal-title":"Nature Med."},{"key":"BFnature11444_CR31","doi-asserted-by":"publisher","first-page":"46","DOI":"10.1210\/en.2008-0404","volume":"150","author":"JA Herlein","year":"2009","unstructured":"Herlein, J. A., Fink, B. D., O'Malley, Y. & Sivitz, W. I. Superoxide and respiratory coupling in mitochondria of insulin-deficient diabetic rats. Endocrinology 150, 46\u201355 (2009)","journal-title":"Endocrinology"}],"container-title":["Nature"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/www.nature.com\/articles\/nature11444.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"http:\/\/www.nature.com\/articles\/nature11444","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"http:\/\/www.nature.com\/articles\/nature11444.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,5,18]],"date-time":"2023-05-18T14:04:05Z","timestamp":1684418645000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.nature.com\/articles\/nature11444"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2012,10,10]]},"references-count":31,"journal-issue":{"issue":"7423","published-print":{"date-parts":[[2012,11,8]]}},"alternative-id":["BFnature11444"],"URL":"https:\/\/doi.org\/10.1038\/nature11444","relation":{"has-review":[{"id-type":"doi","id":"10.3410\/f.717964015.793466513","asserted-by":"object"}]},"ISSN":["0028-0836","1476-4687"],"issn-type":[{"value":"0028-0836","type":"print"},{"value":"1476-4687","type":"electronic"}],"subject":[],"published":{"date-parts":[[2012,10,10]]},"assertion":[{"value":"6 April 2010","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"26 July 2012","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"10 October 2012","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"M.E.A. is a named inventor on patents claiming to treat heart disease by CaMKII inhibition. He is a founder and advisor to Allosteros Therapeutics. At present no income derives from these activities.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}]}}