{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,4]],"date-time":"2026-09-04T20:03:26Z","timestamp":1788552206055,"version":"build-2803163510"},"reference-count":77,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2025,7,23]],"date-time":"2025-07-23T00:00:00Z","timestamp":1753228800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0"},{"start":{"date-parts":[[2025,7,23]],"date-time":"2025-07-23T00:00:00Z","timestamp":1753228800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0"}],"funder":[{"DOI":"10.13039\/100000057","name":"U.S. Department of Health & Human Services | NIH | National Institute of General Medical Sciences","doi-asserted-by":"publisher","award":["R01GM145674"],"award-info":[{"award-number":["R01GM145674"]}],"id":[{"id":"10.13039\/100000057","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Commun Biol"],"DOI":"10.1038\/s42003-025-08475-0","type":"journal-article","created":{"date-parts":[[2025,7,23]],"date-time":"2025-07-23T07:18:14Z","timestamp":1753255094000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Sepsis restructures the mitochondrial calcium uniporter complex in the lymphoid tissues of mice and humans"],"prefix":"10.1038","volume":"8","author":[{"given":"Xianghong","family":"Zhang","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jianguo","family":"Lin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Baobo","family":"Zou","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jack R.","family":"Killinger","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1108-3895","authenticated-orcid":false,"given":"Andrew C.","family":"Sayce","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thiagarajan","family":"Meyyappan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zeyu","family":"Xiong","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6864-5970","authenticated-orcid":false,"given":"Melanie J.","family":"Scott","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6812-6043","authenticated-orcid":false,"given":"Janet S.","family":"Lee","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9203-5478","authenticated-orcid":false,"given":"Matthew R.","family":"Rosengart","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2025,7,23]]},"reference":[{"key":"8475_CR1","doi-asserted-by":"publisher","first-page":"1241","DOI":"10.1001\/jama.2017.13836","volume":"318","author":"C Rhee","year":"2017","unstructured":"Rhee, C. et al. Incidence and trends of sepsis in US hospitals using clinical vs claims data, 2009-2014. JAMA 318, 1241\u20131249 (2017).","journal-title":"JAMA"},{"key":"8475_CR2","unstructured":"CDC. https:\/\/www.cdc.gov\/sepsis\/datareports\/index.html (2018)."},{"key":"8475_CR3","doi-asserted-by":"publisher","first-page":"259","DOI":"10.1164\/rccm.201504-0781OC","volume":"193","author":"C Fleischmann","year":"2016","unstructured":"Fleischmann, C. et al. Assessment of global incidence and mortality of hospital-treated sepsis. Current estimates and limitations. Am. J. Respir. Crit. Care Med 193, 259\u2013272 (2016).","journal-title":"Am. J. Respir. Crit. Care Med"},{"key":"8475_CR4","doi-asserted-by":"publisher","first-page":"1108","DOI":"10.1111\/j.1532-5415.2005.53352.x","volume":"53","author":"ES O\u2019Meara","year":"2005","unstructured":"O\u2019Meara, E. S., White, M., Siscovick, D. S., Lyles, M. F. & Kuller, L. H. Hospitalization for pneumonia in the Cardiovascular Health Study: incidence, mortality, and influence on longer-term survival. J. Am. Geriatr. Soc. 53, 1108\u20131116 (2005).","journal-title":"J. Am. Geriatr. Soc."},{"key":"8475_CR5","doi-asserted-by":"publisher","first-page":"30","DOI":"10.1016\/0140-6736(93)91887-R","volume":"342","author":"FL Brancati","year":"1993","unstructured":"Brancati, F. L., Chow, J. W., Wagener, M. M., Vacarello, S. J. & Yu, V. L. Is pneumonia really the old man\u2019s friend? Two-year prognosis after community-acquired pneumonia. Lancet 342, 30\u201333 (1993).","journal-title":"Lancet"},{"key":"8475_CR6","doi-asserted-by":"publisher","first-page":"1550","DOI":"10.1001\/archinte.159.14.1550","volume":"159","author":"I Koivula","year":"1999","unstructured":"Koivula, I., Sten, M. & Makela, P. H. Prognosis after community-acquired pneumonia in the elderly: a population-based 12-year follow-up study. Arch. Intern Med. 159, 1550\u20131555 (1999).","journal-title":"Arch. Intern Med."},{"key":"8475_CR7","doi-asserted-by":"publisher","first-page":"518","DOI":"10.1111\/j.1532-5415.2007.01100.x","volume":"55","author":"S Yende","year":"2007","unstructured":"Yende, S. et al. Influence of comorbid conditions on long-term mortality after pneumonia in older people. J. Am. Geriatr. Soc. 55, 518\u2013525 (2007).","journal-title":"J. Am. Geriatr. Soc."},{"key":"8475_CR8","doi-asserted-by":"publisher","first-page":"e004283","DOI":"10.1136\/bmjopen-2013-004283","volume":"4","author":"HE Wang","year":"2014","unstructured":"Wang, H. E. et al. Long-term mortality after community-acquired sepsis: a longitudinal population-based cohort study. BMJ Open 4, e004283 (2014).","journal-title":"BMJ Open"},{"key":"8475_CR9","doi-asserted-by":"publisher","first-page":"e22847","DOI":"10.1371\/journal.pone.0022847","volume":"6","author":"S Yende","year":"2011","unstructured":"Yende, S. et al. Elevated hemostasis markers after pneumonia increases one-year risk of all-cause and cardiovascular deaths. PloS One 6, e22847 (2011).","journal-title":"PloS One"},{"key":"8475_CR10","doi-asserted-by":"publisher","first-page":"78","DOI":"10.1007\/s00134-018-5173-1","volume":"45","author":"RT Mankowski","year":"2019","unstructured":"Mankowski, R. T., Yende, S. & Angus, D. C. Long-term impact of sepsis on cardiovascular health. Intensive Care Med. 45, 78\u201381 (2019).","journal-title":"Intensive Care Med."},{"key":"8475_CR11","doi-asserted-by":"publisher","first-page":"1242","DOI":"10.1164\/rccm.200712-1777OC","volume":"177","author":"S Yende","year":"2008","unstructured":"Yende, S. et al. Inflammatory markers at hospital discharge predict subsequent mortality after pneumonia and sepsis. Am. J. Respir. Crit. Care Med. 177, 1242\u20131247 (2008).","journal-title":"Am. J. Respir. Crit. Care Med."},{"key":"8475_CR12","doi-asserted-by":"publisher","first-page":"566","DOI":"10.1038\/nrm3412","volume":"13","author":"R Rizzuto","year":"2012","unstructured":"Rizzuto, R., De Stefani, D., Raffaello, A. & Mammucari, C. Mitochondria as sensors and regulators of calcium signalling. Nat. Rev. Mol. Cell Biol. 13, 566\u2013578 (2012).","journal-title":"Nat. Rev. Mol. Cell Biol."},{"key":"8475_CR13","doi-asserted-by":"publisher","first-page":"10527","DOI":"10.1016\/S0021-9258(18)86979-4","volume":"265","author":"AN Murphy","year":"1990","unstructured":"Murphy, A. N., Kelleher, J. K. & Fiskum, G. Submicromolar Ca2+ regulates phosphorylating respiration by normal rat liver and AS-30D hepatoma mitochondria by different mechanisms. J. Biol. Chem. 265, 10527\u201310534 (1990).","journal-title":"J. Biol. Chem."},{"key":"8475_CR14","doi-asserted-by":"publisher","first-page":"1018","DOI":"10.1016\/j.bbabio.2010.02.005","volume":"1797","author":"FN Gellerich","year":"2010","unstructured":"Gellerich, F. N. et al. The regulation of OXPHOS by extramitochondrial calcium. Biochim. Biophys. Acta 1797, 1018\u20131027 (2010).","journal-title":"Biochim. Biophys. Acta"},{"key":"8475_CR15","doi-asserted-by":"publisher","first-page":"391","DOI":"10.1152\/physrev.1990.70.2.391","volume":"70","author":"JG McCormack","year":"1990","unstructured":"McCormack, J. G., Halestrap, A. P. & Denton, R. M. Role of calcium ions in regulation of mammalian intramitochondrial metabolism. Physiol. Rev. 70, 391\u2013425 (1990).","journal-title":"Physiol. Rev."},{"key":"8475_CR16","doi-asserted-by":"publisher","first-page":"907","DOI":"10.1016\/j.bbabio.2010.01.005","volume":"1797","author":"J Santo-Domingo","year":"2010","unstructured":"Santo-Domingo, J. & Demaurex, N. Calcium uptake mechanisms of mitochondria. Biochim. Biophys. Acta 1797, 907\u2013912 (2010).","journal-title":"Biochim. Biophys. Acta"},{"key":"8475_CR17","doi-asserted-by":"publisher","first-page":"1374","DOI":"10.1016\/j.bbabio.2009.01.007","volume":"1787","author":"C Walsh","year":"2009","unstructured":"Walsh, C. et al. Modulation of calcium signalling by mitochondria. Biochim. Biophys. Acta 1787, 1374\u20131382 (2009).","journal-title":"Biochim. Biophys. Acta"},{"key":"8475_CR18","doi-asserted-by":"publisher","first-page":"86","DOI":"10.1016\/j.ceca.2018.06.006","volume":"74","author":"N Nemani","year":"2018","unstructured":"Nemani, N., Shanmughapriya, S. & Madesh, M. Molecular regulation of MCU: implications in physiology and disease. Cell Calcium 74, 86\u201393 (2018).","journal-title":"Cell Calcium"},{"key":"8475_CR19","doi-asserted-by":"publisher","first-page":"139","DOI":"10.1016\/j.ceca.2014.02.008","volume":"55","author":"D Pendin","year":"2014","unstructured":"Pendin, D., Greotti, E. & Pozzan, T. The elusive importance of being a mitochondrial Ca(2+) uniporter. Cell Calcium 55, 139\u2013145 (2014).","journal-title":"Cell Calcium"},{"key":"8475_CR20","doi-asserted-by":"publisher","first-page":"2457","DOI":"10.1016\/j.bbamcr.2016.03.006","volume":"1863","author":"C Mammucari","year":"2016","unstructured":"Mammucari, C., Raffaello, A., Vecellio Reane, D. & Rizzuto, R. Molecular structure and pathophysiological roles of the Mitochondrial Calcium Uniporter. Biochim. Biophys. Acta 1863, 2457\u20132464 (2016).","journal-title":"Biochim. Biophys. Acta"},{"key":"8475_CR21","doi-asserted-by":"publisher","first-page":"10479","DOI":"10.1073\/pnas.1300410110","volume":"110","author":"GS Williams","year":"2013","unstructured":"Williams, G. S., Boyman, L., Chikando, A. C., Khairallah, R. J. & Lederer, W. J. Mitochondrial calcium uptake. Proc. Natl. Acad. Sci. USA 110, 10479\u201310486 (2013).","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"8475_CR22","doi-asserted-by":"publisher","first-page":"2006","DOI":"10.1016\/j.bbamcr.2015.04.008","volume":"1853","author":"D De Stefani","year":"2015","unstructured":"De Stefani, D., Patron, M. & Rizzuto, R. Structure and function of the mitochondrial calcium uniporter complex. Biochim. Biophys. Acta 1853, 2006\u20132011 (2015).","journal-title":"Biochim. Biophys. Acta"},{"key":"8475_CR23","doi-asserted-by":"publisher","first-page":"829","DOI":"10.1113\/jphysiol.2013.268235","volume":"592","author":"S Marchi","year":"2014","unstructured":"Marchi, S. & Pinton, P. The mitochondrial calcium uniporter complex: molecular components, structure and physiopathological implications. J. Physiol. 592, 829\u2013839 (2014).","journal-title":"J. Physiol."},{"key":"8475_CR24","doi-asserted-by":"publisher","first-page":"1561","DOI":"10.1016\/j.celrep.2016.07.011","volume":"16","author":"JC Liu","year":"2016","unstructured":"Liu, J. C. et al. MICU1 serves as a molecular gatekeeper to prevent in vivo mitochondrial calcium overload. Cell Rep. 16, 1561\u20131573 (2016).","journal-title":"Cell Rep."},{"key":"8475_CR25","doi-asserted-by":"publisher","first-page":"630","DOI":"10.1016\/j.cell.2012.10.011","volume":"151","author":"K Mallilankaraman","year":"2012","unstructured":"Mallilankaraman, K. et al. MICU1 is an essential gatekeeper for MCU-mediated mitochondrial Ca(2+) uptake that regulates cell survival. Cell 151, 630\u2013644 (2012).","journal-title":"Cell"},{"key":"8475_CR26","doi-asserted-by":"publisher","first-page":"976","DOI":"10.1016\/j.cmet.2013.04.020","volume":"17","author":"G Csordas","year":"2013","unstructured":"Csordas, G. et al. MICU1 controls both the threshold and cooperative activation of the mitochondrial Ca(2)(+) uniporter. Cell Metab. 17, 976\u2013987 (2013).","journal-title":"Cell Metab."},{"key":"8475_CR27","doi-asserted-by":"publisher","DOI":"10.1038\/ncomms10955","volume":"7","author":"AN Antony","year":"2016","unstructured":"Antony, A. N. et al. MICU1 regulation of mitochondrial Ca(2+) uptake dictates survival and tissue regeneration. Nat. Commun. 7, 10955 (2016).","journal-title":"Nat. Commun."},{"key":"8475_CR28","doi-asserted-by":"publisher","first-page":"1110","DOI":"10.1016\/j.bbamem.2016.02.022","volume":"1858","author":"J Matesanz-Isabel","year":"2016","unstructured":"Matesanz-Isabel, J. et al. Functional roles of MICU1 and MICU2 in mitochondrial Ca(2+) uptake. Biochim. Biophys. Acta 1858, 1110\u20131117 (2016).","journal-title":"Biochim. Biophys. Acta"},{"key":"8475_CR29","doi-asserted-by":"publisher","first-page":"726","DOI":"10.1016\/j.molcel.2014.01.013","volume":"53","author":"M Patron","year":"2014","unstructured":"Patron, M. et al. MICU1 and MICU2 finely tune the mitochondrial Ca2+ uniporter by exerting opposite effects on MCU activity. Mol. Cell 53, 726\u2013737 (2014).","journal-title":"Mol. Cell"},{"key":"8475_CR30","doi-asserted-by":"publisher","first-page":"eabj4716","DOI":"10.1126\/sciadv.abj4716","volume":"8","author":"R Singh","year":"2022","unstructured":"Singh, R. et al. Uncontrolled mitochondrial calcium uptake underlies the pathogenesis of neurodegeneration in MICU1-deficient mice and patients. Sci. Adv. 8, eabj4716 (2022).","journal-title":"Sci. Adv."},{"key":"8475_CR31","doi-asserted-by":"publisher","first-page":"188","DOI":"10.1038\/ng.2851","volume":"46","author":"CV Logan","year":"2014","unstructured":"Logan, C. V. et al. Loss-of-function mutations in MICU1 cause a brain and muscle disorder linked to primary alterations in mitochondrial calcium signaling. Nat. Genet. 46, 188\u2013193 (2014).","journal-title":"Nat. Genet."},{"key":"8475_CR32","doi-asserted-by":"publisher","first-page":"1336","DOI":"10.1038\/ncb2622","volume":"14","author":"K Mallilankaraman","year":"2012","unstructured":"Mallilankaraman, K. et al. MCUR1 is an essential component of mitochondrial Ca2+ uptake that regulates cellular metabolism. Nat. Cell Biol. 14, 1336\u20131343 (2012).","journal-title":"Nat. Cell Biol."},{"key":"8475_CR33","doi-asserted-by":"publisher","first-page":"1264","DOI":"10.1046\/j.1399-6576.2003.00236.x","volume":"47","author":"J Hastbacka","year":"2003","unstructured":"Hastbacka, J. & Pettila, V. Prevalence and predictive value of ionized hypocalcemia among critically ill patients. Acta Anaesthesiol. Scand. 47, 1264\u20131269 (2003).","journal-title":"Acta Anaesthesiol. Scand."},{"key":"8475_CR34","doi-asserted-by":"publisher","first-page":"149","DOI":"10.1042\/bss0660149","volume":"66","author":"M Singer","year":"1999","unstructured":"Singer, M. & Brealey, D. Mitochondrial dysfunction in sepsis. Biochem Soc. Symp. 66, 149\u2013166 (1999).","journal-title":"Biochem Soc. Symp."},{"key":"8475_CR35","doi-asserted-by":"publisher","first-page":"S441","DOI":"10.1097\/01.CCM.0000278049.48333.78","volume":"35","author":"M Singer","year":"2007","unstructured":"Singer, M. Mitochondrial function in sepsis: acute phase versus multiple organ failure. Crit. Care Med. 35, S441\u2013S448 (2007).","journal-title":"Crit. Care Med."},{"key":"8475_CR36","doi-asserted-by":"publisher","first-page":"297","DOI":"10.1016\/j.jss.2013.08.007","volume":"186","author":"SP Whelan","year":"2014","unstructured":"Whelan, S. P. et al. Polymicrobial sepsis is associated with decreased hepatic oxidative phosphorylation and an altered metabolic profile. J. Surg. Res. 186, 297\u2013303 (2014).","journal-title":"J. Surg. Res."},{"key":"8475_CR37","doi-asserted-by":"publisher","first-page":"729","DOI":"10.1016\/j.mito.2004.07.023","volume":"4","author":"ED Crouser","year":"2004","unstructured":"Crouser, E. D. Mitochondrial dysfunction in septic shock and multiple organ dysfunction syndrome. Mitochondrion 4, 729\u2013741 (2004).","journal-title":"Mitochondrion"},{"key":"8475_CR38","doi-asserted-by":"publisher","first-page":"664","DOI":"10.1097\/SLA.0000000000005067","volume":"274","author":"DB Darden","year":"2021","unstructured":"Darden, D. B. et al. Biomarker evidence of the persistent inflammation, immunosuppression and catabolism syndrome (PICS) in chronic critical illness (CCI) after surgical sepsis. Ann. Surg. 274, 664\u2013673 (2021).","journal-title":"Ann. Surg."},{"key":"8475_CR39","doi-asserted-by":"publisher","first-page":"1511","DOI":"10.3389\/fimmu.2018.01511","volume":"9","author":"RB Hawkins","year":"2018","unstructured":"Hawkins, R. B. et al. Chronic critical illness and the persistent inflammation, immunosuppression, and catabolism syndrome. Front Immunol. 9, 1511 (2018).","journal-title":"Front Immunol."},{"key":"8475_CR40","doi-asserted-by":"publisher","first-page":"285","DOI":"10.4049\/jimmunol.155.1.285","volume":"155","author":"KL Bost","year":"1995","unstructured":"Bost, K. L. & Mason, M. J. Thapsigargin and cyclopiazonic acid initiate rapid and dramatic increases of IL-6 mRNA expression and IL-6 secretion in murine peritoneal macrophages. J. Immunol. 155, 285\u2013296 (1995).","journal-title":"J. Immunol."},{"key":"8475_CR41","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1089\/sur.2016.261","volume":"18","author":"JE Mazuski","year":"2017","unstructured":"Mazuski, J. E. et al. The surgical infection society revised guidelines on the management of intra-abdominal infection. Surg. Infect. 18, 1\u201376 (2017).","journal-title":"Surg. Infect."},{"key":"8475_CR42","doi-asserted-by":"publisher","first-page":"829","DOI":"10.1056\/NEJMoa1711584","volume":"378","author":"MW Semler","year":"2018","unstructured":"Semler, M. W. et al. Balanced crystalloids versus saline in critically ill adults. N. Engl. J. Med. 378, 829\u2013839 (2018).","journal-title":"N. Engl. J. Med."},{"key":"8475_CR43","doi-asserted-by":"publisher","first-page":"1996","DOI":"10.1056\/NEJMoa1411162","volume":"372","author":"RG Sawyer","year":"2015","unstructured":"Sawyer, R. G. et al. Trial of short-course antimicrobial therapy for intraabdominal infection. N. Engl. J. Med. 372, 1996\u20132005 (2015).","journal-title":"N. Engl. J. Med."},{"key":"8475_CR44","doi-asserted-by":"publisher","first-page":"2291","DOI":"10.1016\/j.celrep.2017.02.032","volume":"18","author":"M Paillard","year":"2017","unstructured":"Paillard, M. et al. Tissue-specific mitochondrial decoding of cytoplasmic Ca(2+) signals is controlled by the stoichiometry of MICU1\/2 and MCU. Cell Rep. 18, 2291\u20132300 (2017).","journal-title":"Cell Rep."},{"key":"8475_CR45","doi-asserted-by":"publisher","DOI":"10.3389\/fphys.2020.554904","volume":"11","author":"G Gherardi","year":"2020","unstructured":"Gherardi, G., Monticelli, H., Rizzuto, R. & Mammucari, C. The mitochondrial Ca(2+) uptake and the fine-tuning of aerobic metabolism. Front. Physiol. 11, 554904 (2020).","journal-title":"Front. Physiol."},{"key":"8475_CR46","doi-asserted-by":"publisher","first-page":"2959","DOI":"10.1021\/bi2018909","volume":"51","author":"B Glancy","year":"2012","unstructured":"Glancy, B. & Balaban, R. S. Role of mitochondrial Ca2+ in the regulation of cellular energetics. Biochemistry 51, 2959\u20132973 (2012).","journal-title":"Biochemistry"},{"key":"8475_CR47","doi-asserted-by":"publisher","first-page":"11282","DOI":"10.1073\/pnas.1117765109","volume":"109","author":"T Murakami","year":"2012","unstructured":"Murakami, T. et al. Critical role for calcium mobilization in activation of the NLRP3 inflammasome. Proc. Natl. Acad. Sci. USA 109, 11282\u201311287 (2012).","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"8475_CR48","doi-asserted-by":"publisher","first-page":"119","DOI":"10.2174\/156652408783769571","volume":"8","author":"C Giorgi","year":"2008","unstructured":"Giorgi, C., Romagnoli, A., Pinton, P. & Rizzuto, R. Ca2+ signaling, mitochondria and cell death. Curr. Mol. Med. 8, 119\u2013130 (2008).","journal-title":"Curr. Mol. Med."},{"key":"8475_CR49","doi-asserted-by":"publisher","DOI":"10.1038\/s41580-018-0052-8","author":"C Giorgi","year":"2018","unstructured":"Giorgi, C., Marchi, S. & Pinton, P. The machineries, regulation and cellular functions of mitochondrial calcium. Nat. Rev. Mol. Cell Biol. https:\/\/doi.org\/10.1038\/s41580-018-0052-8 (2018).","journal-title":"Nat. Rev. Mol. Cell Biol."},{"key":"8475_CR50","doi-asserted-by":"publisher","first-page":"181","DOI":"10.4161\/auto.3678","volume":"3","author":"DJ Klionsky","year":"2007","unstructured":"Klionsky, D. J., Cuervo, A. M. & Seglen, P. O. Methods for monitoring autophagy from yeast to human. Autophagy 3, 181\u2013206 (2007).","journal-title":"Autophagy"},{"key":"8475_CR51","doi-asserted-by":"publisher","first-page":"663","DOI":"10.1042\/EBC20170057","volume":"61","author":"S Catarino","year":"2017","unstructured":"Catarino, S., Pereira, P. & Girao, H. Molecular control of chaperone-mediated autophagy. Essays Biochem. 61, 663\u2013674 (2017).","journal-title":"Essays Biochem."},{"key":"8475_CR52","doi-asserted-by":"publisher","first-page":"365","DOI":"10.1038\/s41580-018-0001-6","volume":"19","author":"S Kaushik","year":"2018","unstructured":"Kaushik, S. & Cuervo, A. M. The coming of age of chaperone-mediated autophagy. Nat. Rev. Mol. Cell Biol. 19, 365\u2013381 (2018).","journal-title":"Nat. Rev. Mol. Cell Biol."},{"key":"8475_CR53","doi-asserted-by":"publisher","first-page":"3493","DOI":"10.1021\/acs.jmedchem.0c01689","volume":"64","author":"J Pei","year":"2021","unstructured":"Pei, J. et al. Targeting lysosomal degradation pathways: new strategies and techniques for drug discovery. J. Med. Chem. 64, 3493\u20133507 (2021).","journal-title":"J. Med. Chem."},{"key":"8475_CR54","doi-asserted-by":"publisher","unstructured":"Wang, H., Zhu, Y., Liu, H., Liang, T. & Wei, Y. Advances in Drug Discovery Targeting Lysosomal Membrane Proteins. Pharmaceuticals 16, https:\/\/doi.org\/10.3390\/ph16040601 (2023).","DOI":"10.3390\/ph16040601"},{"key":"8475_CR55","doi-asserted-by":"publisher","first-page":"1276","DOI":"10.1097\/CCM.0b013e3181d8cc1d","volume":"38","author":"BD Winters","year":"2010","unstructured":"Winters, B. D. et al. Long-term mortality and quality of life in sepsis: a systematic review. Crit. Care Med. 38, 1276\u20131283 (2010).","journal-title":"Crit. Care Med."},{"key":"8475_CR56","doi-asserted-by":"publisher","DOI":"10.1186\/s13613-022-01038-0","volume":"12","author":"G Voiriot","year":"2022","unstructured":"Voiriot, G. et al. Chronic critical illness and post-intensive care syndrome: from pathophysiology to clinical challenges. Ann. Intensive Care 12, 58 (2022).","journal-title":"Ann. Intensive Care"},{"key":"8475_CR57","doi-asserted-by":"publisher","first-page":"253","DOI":"10.1097\/CCM.0000000000002074","volume":"45","author":"JC Mira","year":"2017","unstructured":"Mira, J. C. et al. Sepsis pathophysiology, chronic critical illness, and persistent inflammation-immunosuppression and catabolism syndrome. Crit. Care Med. 45, 253\u2013262 (2017).","journal-title":"Crit. Care Med."},{"key":"8475_CR58","doi-asserted-by":"publisher","first-page":"1491","DOI":"10.1097\/TA.0b013e318256e000","volume":"72","author":"LF Gentile","year":"2012","unstructured":"Gentile, L. F. et al. Persistent inflammation and immunosuppression: a common syndrome and new horizon for surgical intensive care. J. Trauma Acute Care Surg. 72, 1491\u20131501 (2012).","journal-title":"J. Trauma Acute Care Surg."},{"key":"8475_CR59","doi-asserted-by":"publisher","first-page":"595","DOI":"10.3389\/fimmu.2018.00595","volume":"9","author":"H Horiguchi","year":"2018","unstructured":"Horiguchi, H. et al. Innate immunity in the persistent inflammation, immunosuppression, and catabolism syndrome and its implications for therapy. Front. Immunol. 9, 595 (2018).","journal-title":"Front. Immunol."},{"key":"8475_CR60","doi-asserted-by":"publisher","first-page":"2617","DOI":"10.1046\/j.1471-4159.1999.0722617.x","volume":"72","author":"SA Anderson","year":"1999","unstructured":"Anderson, S. A., Song, S. K., Ackerman, J. J. & Hotchkiss, R. S. Sepsis increases intracellular free calcium in brain. J. Neurochem. 72, 2617\u20132620 (1999).","journal-title":"J. Neurochem."},{"key":"8475_CR61","doi-asserted-by":"publisher","first-page":"598","DOI":"10.1097\/01.CCM.0000152223.27176.A6","volume":"33","author":"X Zhu","year":"2005","unstructured":"Zhu, X. et al. Increased leakage of sarcoplasmic reticulum Ca2+ contributes to abnormal myocyte Ca2+ handling and shortening in sepsis. Crit. Care Med. 33, 598\u2013604 (2005).","journal-title":"Crit. Care Med."},{"key":"8475_CR62","doi-asserted-by":"publisher","first-page":"e352","DOI":"10.1097\/CCM.0b013e31828cf436","volume":"41","author":"RD Collage","year":"2013","unstructured":"Collage, R. D. et al. Calcium supplementation during sepsis exacerbates organ failure and mortality via calcium\/calmodulin-dependent protein kinase kinase signaling. Crit. Care Med. 41, e352\u2013e360 (2013).","journal-title":"Crit. Care Med."},{"key":"8475_CR63","doi-asserted-by":"publisher","first-page":"3933","DOI":"10.1073\/pnas.90.9.3933","volume":"90","author":"SK Song","year":"1993","unstructured":"Song, S. K., Karl, I. E., Ackerman, J. J. & Hotchkiss, R. S. Increased intracellular Ca2+: a critical link in the pathophysiology of sepsis?. Proc. Natl. Acad. Sci. USA 90, 3933\u20133937 (1993).","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"8475_CR64","doi-asserted-by":"publisher","first-page":"e840","DOI":"10.1097\/CCM.0000000000002448","volume":"45","author":"BB Pinto","year":"2017","unstructured":"Pinto, B. B. et al. Improved survival in a long-term rat model of sepsis is associated with reduced mitochondrial calcium uptake despite increased energetic demand. Crit. Care Med. 45, e840\u2013e848 (2017).","journal-title":"Crit. Care Med."},{"key":"8475_CR65","doi-asserted-by":"publisher","first-page":"249","DOI":"10.1189\/jlb.0510286","volume":"90","author":"X Zhang","year":"2011","unstructured":"Zhang, X. et al. Calcium\/calmodulin-dependent protein kinase (CaMK) Ialpha mediates the macrophage inflammatory response to sepsis. J. Leukoc. Biol. 90, 249\u2013261 (2011).","journal-title":"J. Leukoc. Biol."},{"key":"8475_CR66","doi-asserted-by":"crossref","unstructured":"Zhang, X. et al. CaMKIV-dependent preservation of mTOR expression is required for autophagy during LPS-induced inflammation and acute kidney injury. J. Immunol. 193, 2405\u20132415 (2014).","DOI":"10.4049\/jimmunol.1302798"},{"key":"8475_CR67","doi-asserted-by":"publisher","first-page":"5015","DOI":"10.4049\/jimmunol.181.7.5015","volume":"181","author":"X Zhang","year":"2008","unstructured":"Zhang, X. et al. Calcium\/calmodulin-dependent protein kinase (CaMK) IV mediates nucleocytoplasmic shuttling and release of HMGB1 during lipopolysaccharide stimulation of macrophages. J. Immunol. 181, 5015\u20135023 (2008).","journal-title":"J. Immunol."},{"key":"8475_CR68","doi-asserted-by":"publisher","first-page":"4382","DOI":"10.1096\/fj.201601096RRR","volume":"31","author":"X Zhang","year":"2017","unstructured":"Zhang, X. et al. Calcium\/calmodulin-dependent protein kinase regulates the PINK1\/Parkin and DJ-1 pathways of mitophagy during sepsis. FASEB J. 31, 4382\u20134395 (2017).","journal-title":"FASEB J."},{"key":"8475_CR69","doi-asserted-by":"publisher","first-page":"102286","DOI":"10.1016\/j.ceca.2020.102286","volume":"92","author":"X Zhang","year":"2020","unstructured":"Zhang, X. et al. CaMKIV regulates mitochondrial dynamics during sepsis. Cell Calcium 92, 102286 (2020).","journal-title":"Cell Calcium"},{"key":"8475_CR70","doi-asserted-by":"publisher","first-page":"32","DOI":"10.1097\/TA.0000000000004293","volume":"97","author":"S Taghavi","year":"2024","unstructured":"Taghavi, S. et al. Dimethyl sulfoxide as a novel therapy in a murine model of acute lung injury. J. Trauma Acute Care Surg. 97, 32\u201338 (2024).","journal-title":"J. Trauma Acute Care Surg."},{"key":"8475_CR71","doi-asserted-by":"publisher","first-page":"10853","DOI":"10.3748\/wjg.v21.i38.10853","volume":"21","author":"YM Li","year":"2015","unstructured":"Li, Y. M. et al. Dimethyl sulfoxide inhibits zymosan-induced intestinal inflammation and barrier dysfunction. World J. Gastroenterol. 21, 10853\u201310865 (2015).","journal-title":"World J. Gastroenterol."},{"key":"8475_CR72","doi-asserted-by":"publisher","unstructured":"Evankovich, J. et al. Calcium\/Calmodulin-Dependent Protein Kinase IV limits organ damage in hepatic ischemia\/reperfusion injury through induction of autophagy. Am. J. Physiol. https:\/\/doi.org\/10.1152\/ajpgi.00051.2012 (2012).","DOI":"10.1152\/ajpgi.00051.2012"},{"key":"8475_CR73","doi-asserted-by":"publisher","first-page":"573","DOI":"10.1038\/nn0602-855","volume":"5","author":"F Wei","year":"2002","unstructured":"Wei, F. et al. Calcium calmodulin-dependent protein kinase IV is required for fear memory. Nat. Neurosci. 5, 573\u2013579 (2002).","journal-title":"Nat. Neurosci."},{"key":"8475_CR74","doi-asserted-by":"publisher","first-page":"2405","DOI":"10.4049\/jimmunol.1302798","volume":"193","author":"X Zhang","year":"2014","unstructured":"Zhang, X. et al. CaMKIV-dependent preservation of mTOR expression is required for autophagy during lipopolysaccharide-induced inflammation and acute kidney injury. J. Immunol. 193, 2405\u20132415 (2014).","journal-title":"J. Immunol."},{"key":"8475_CR75","doi-asserted-by":"publisher","first-page":"52","DOI":"10.1097\/01.shk.0000191414.94461.7e","volume":"24","author":"WJ Hubbard","year":"2005","unstructured":"Hubbard, W. J. et al. Cecal ligation and puncture. Shock 24, 52\u201357 (2005).","journal-title":"Shock"},{"key":"8475_CR76","doi-asserted-by":"publisher","unstructured":"Griepentrog, J. E. et al. Frontline Science: Rev-Erbalpha links blue light with enhanced bacterial clearance and improved survival in murine Klebsiella pneumoniae pneumonia. J. Leukocyte Biol. https:\/\/doi.org\/10.1002\/JLB.4HI0519-155R (2019).","DOI":"10.1002\/JLB.4HI0519-155R"},{"key":"8475_CR77","doi-asserted-by":"publisher","unstructured":"Zhang, X. et al. Sepsis restructures the mitochondrial calcium uniporter complex in the lymphoid tissues of mice and humans [Dataset]. Dryad, https:\/\/doi.org\/10.5061\/dryad.573n5tbkz (2025).","DOI":"10.5061\/dryad.573n5tbkz"}],"container-title":["Communications Biology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.nature.com\/articles\/s42003-025-08475-0.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s42003-025-08475-0","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s42003-025-08475-0.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,9,7]],"date-time":"2025-09-07T23:01:11Z","timestamp":1757286071000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.nature.com\/articles\/s42003-025-08475-0"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,7,23]]},"references-count":77,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2025,12]]}},"alternative-id":["8475"],"URL":"https:\/\/doi.org\/10.1038\/s42003-025-08475-0","relation":{},"ISSN":["2399-3642"],"issn-type":[{"value":"2399-3642","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,7,23]]},"assertion":[{"value":"14 August 2024","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"2 July 2025","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"23 July 2025","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"The authors declare no competing interests.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"1093"}}