{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,14]],"date-time":"2026-09-14T13:18:55Z","timestamp":1789391935164,"version":"build-2803163510"},"reference-count":61,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2023,3,13]],"date-time":"2023-03-13T00:00:00Z","timestamp":1678665600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82172127 81772036 82072144 81671952 81873950 81873953 82030059"],"award-info":[{"award-number":["82172127 81772036 82072144 81671952 81873950 81873953 82030059"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100012166","name":"National Key Research and Development Program of China","doi-asserted-by":"publisher","award":["2020YFC1512700 2020YFC1512705 2020YFC1512703 2020YFC0846600"],"award-info":[{"award-number":["2020YFC1512700 2020YFC1512705 2020YFC1512703 2020YFC0846600"]}],"id":[{"id":"10.13039\/501100012166","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100012620","name":"Taishan Scholar Foundation of Shandong Province","doi-asserted-by":"publisher","award":["tspd20181220 tsqn20161065 tsqn201812129"],"award-info":[{"award-number":["tspd20181220 tsqn20161065 tsqn201812129"]}],"id":[{"id":"10.13039\/100012620","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Pharmacol."],"abstract":"<jats:p>Cell survival or death is critical for cardiac function. Myocardial pyroptosis, as a newly recognized programmed cell death, remains poorly understood in sepsis. In this study, we evaluated the effect of aldehyde dehydrogenase (ALDH2) on myocardial pyroptosis and revealed the underlying mechanisms in sepsis. We established a septic shock mice model by intraperitoneal injection of Lipopolysaccharide (LPS, 15\u00a0mg\/kg) 12\u00a0h before sacrifice. It was found that aldehyde dehydrogenase significantly inhibited NOD-like receptor protein 3 (NLRP3) inflammasome activation and Caspase-1\/GSDMD-dependent pyroptosis, which remarkably improved survival rate and septic shock-induced cardiac dysfunction, relative to the control group. While aldehyde dehydrogenase knockout or knockdown significantly aggravated these phenomena. Intriguingly, we found that aldehyde dehydrogenase inhibited LPS-induced deacetylation of Hydroxyacyl-CoA dehydrogenase trifunctional multienzyme complex \u03b1 subunit (HADHA) by suppressing the translocation of Histone deacetylase 3 (HDAC3) from nuclei to mitochondria. Acetylated HADHA is essential for mitochondrial fatty acid \u03b2-oxidation, and its interruption can result in accumulation of toxic lipids, induce mROS and cause mtDNA and ox-mtDNA release. Our results confirmed the role of Histone deacetylase 3 and HADHA in NOD-like receptor protein 3 inflammasome activation. <jats:italic>Hdac3<\/jats:italic> knockdown remarkedly suppressed NOD-like receptor protein 3 inflammasome and pyroptosis, but <jats:italic>Hadha<\/jats:italic> knockdown eliminated the effect. aldehyde dehydrogenase inhibited the translocation of Histone deacetylase 3, protected ac-HADHA from deacetylation, and significantly reduced the accumulation of toxic aldehyde, and inhibited mROS and ox-mtDNA, thereby avoided NOD-like receptor protein 3 inflammasome activation and pyroptosis. This study provided a novel mechanism of myocardial pyroptosis through mitochondrial Histone deacetylase 3\/HADHA- NOD-like receptor protein 3 inflammasome pathway and demonstrated a significant role of aldehyde dehydrogenase as a therapeutic target for myocardial pyroptosis in sepsis.<\/jats:p>","DOI":"10.3389\/fphar.2023.1125866","type":"journal-article","created":{"date-parts":[[2023,3,13]],"date-time":"2023-03-13T05:23:24Z","timestamp":1678685004000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":22,"title":["ALDH2 attenuates myocardial pyroptosis through breaking down Mitochondrion-NLRP3 inflammasome pathway in septic shock"],"prefix":"10.3389","volume":"14","author":[{"given":"Ying","family":"Zhang","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ying","family":"Lv","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qingju","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xingfang","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qi","family":"Han","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yan","family":"Liang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Simeng","family":"He","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qiuhuan","family":"Yuan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiaqi","family":"Zheng","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Changchang","family":"Xu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiangxin","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zichen","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Huaxiang","family":"Yu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Li","family":"Xue","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiali","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Feng","family":"Xu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiaojiao","family":"Pang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuguo","family":"Chen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2023,3,13]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"269","DOI":"10.1038\/s41569-019-0315-x","article-title":"Reappraising the role of inflammation in heart failure","volume":"17","author":"Adamo","year":"2020","journal-title":"Nat. Rev. Cardiol."},{"key":"B2","doi-asserted-by":"publisher","first-page":"2453","DOI":"10.1093\/eurheartj\/ehaa444","article-title":"Double-edged sword of ALDH2 mutations: One polymorphism can both benefit and harm the cardiovascular system","volume":"41","author":"Bartoli-Leonard","year":"2020","journal-title":"Eur. Heart J."},{"key":"B3","doi-asserted-by":"publisher","first-page":"625","DOI":"10.1097\/CCM.0000000000002851","article-title":"Septic cardiomyopathy","volume":"46","author":"Beesley","year":"2018","journal-title":"Crit. Care Med."},{"key":"B4","doi-asserted-by":"publisher","first-page":"99","DOI":"10.1038\/nrmicro2070","article-title":"Pyroptosis: Host cell death and inflammation","volume":"7","author":"Bergsbaken","year":"2009","journal-title":"Nat. Rev. Microbiol."},{"key":"B5","doi-asserted-by":"publisher","first-page":"407","DOI":"10.1038\/nri.2016.58","article-title":"Inflammasomes: Mechanism of assembly, regulation and signalling","volume":"16","author":"Broz","year":"2016","journal-title":"Nat. Rev. Immunol."},{"key":"B6","doi-asserted-by":"publisher","first-page":"497","DOI":"10.1016\/j.cmet.2018.01.016","article-title":"The mitochondrial acylome emerges: Proteomics, regulation by sirtuins, and metabolic and disease implications","volume":"27","author":"Carrico","year":"2018","journal-title":"Cell Metab."},{"key":"B7","doi-asserted-by":"publisher","first-page":"363","DOI":"10.1111\/imm.13372","article-title":"NLRP7: From inflammasome regulation to human disease","volume":"163","author":"Carriere","year":"2021","journal-title":"Immunology"},{"key":"B8","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1152\/physrev.00017.2013","article-title":"Targeting aldehyde dehydrogenase 2: New therapeutic opportunities","volume":"94","author":"Chen","year":"2014","journal-title":"Physiol. Rev."},{"key":"B9","doi-asserted-by":"publisher","first-page":"E2865","DOI":"10.1073\/pnas.1121131109","article-title":"Requirement for the histone deacetylase Hdac3 for the inflammatory gene expression program in macrophages","volume":"109","author":"Chen","year":"2012","journal-title":"Proc. Natl. Acad. Sci. U. S. A."},{"key":"B10","doi-asserted-by":"publisher","first-page":"43","DOI":"10.1016\/j.molcel.2020.08.015","article-title":"Histone deacetylase 3 couples mitochondria to drive IL-1\u03b2-dependent inflammation by configuring fatty acid oxidation","volume":"80","author":"Chi","year":"2020","journal-title":"Mol. Cell"},{"key":"B11","doi-asserted-by":"publisher","first-page":"1765","DOI":"10.1152\/physrev.00022.2018","article-title":"Fundamental mechanisms of regulated cell death and implications for heart disease","volume":"99","author":"Del Re","year":"2019","journal-title":"Physiol. Rev."},{"key":"B12","doi-asserted-by":"publisher","first-page":"232","DOI":"10.1161\/CIRCRESAHA.120.317933","article-title":"Targeting mitochondria-inflammation circuit by beta-hydroxybutyrate mitigates HFpEF","volume":"128","author":"Deng","year":"2021","journal-title":"Circ. Res."},{"key":"B13","doi-asserted-by":"publisher","first-page":"637","DOI":"10.1016\/j.cmet.2015.03.007","article-title":"SIRT3 mediates multi-tissue coupling for metabolic fuel switching","volume":"21","author":"Dittenhafer-Reed","year":"2015","journal-title":"Cell Metab."},{"key":"B14","doi-asserted-by":"publisher","first-page":"4788","DOI":"10.3390\/ijms21134788","article-title":"The NLRP1 inflammasome in human skin and beyond","volume":"21","author":"Fenini","year":"2020","journal-title":"Int. J. Mol. Sci."},{"key":"B15","doi-asserted-by":"publisher","first-page":"683","DOI":"10.1038\/s41586-019-1770-6","article-title":"Caspase-8 is the molecular switch for apoptosis, necroptosis and pyroptosis","volume":"575","author":"Fritsch","year":"2019","journal-title":"Nature"},{"key":"B16","doi-asserted-by":"publisher","first-page":"156","DOI":"10.1016\/j.jhep.2020.07.041","article-title":"Hepatocyte pyroptosis and release of inflammasome particles induce stellate cell activation and liver fibrosis","volume":"74","author":"Gaul","year":"2021","journal-title":"J. Hepatol."},{"key":"B17","doi-asserted-by":"publisher","first-page":"107","DOI":"10.1146\/annurev-pharmtox-010814-124915","article-title":"A personalized medicine approach for Asian Americans with the aldehyde dehydrogenase 2*2 variant","volume":"55","author":"Gross","year":"2015","journal-title":"Annu. Rev. Pharmacol. Toxicol."},{"key":"B18","doi-asserted-by":"publisher","first-page":"1012","DOI":"10.1016\/j.tibs.2016.09.002","article-title":"Mechanism and regulation of NLRP3 inflammasome activation","volume":"41","author":"He","year":"2016","journal-title":"Trends Biochem. Sci."},{"key":"B19","doi-asserted-by":"publisher","first-page":"424","DOI":"10.1038\/s41569-020-00492-2","article-title":"Pathophysiology of sepsis-induced cardiomyopathy","volume":"18","author":"Hollenberg","year":"2021","journal-title":"Nat. Rev. Cardiol."},{"key":"B20","doi-asserted-by":"publisher","first-page":"23","DOI":"10.1146\/annurev-physiol-021115-105045","article-title":"The biochemistry and Physiology of mitochondrial fatty acid beta-oxidation and its genetic disorders","volume":"78","author":"Houten","year":"2016","journal-title":"Annu. Rev. Physiol."},{"key":"B21","doi-asserted-by":"publisher","first-page":"475","DOI":"10.1016\/j.immuni.2020.02.002","article-title":"mtDNA activates cGAS signaling and suppresses the YAP-mediated endothelial cell proliferation program to promote inflammatory injury","volume":"52","author":"Huang","year":"2020","journal-title":"Immunity"},{"key":"B22","doi-asserted-by":"publisher","first-page":"773","DOI":"10.14336\/AD.2021.1116","article-title":"Histone deacetylase 3: A potential therapeutic target for atherosclerosis","volume":"13","author":"Jiang","year":"2022","journal-title":"Aging Dis."},{"key":"B23","doi-asserted-by":"publisher","first-page":"2989974","DOI":"10.1155\/2021\/2989974","article-title":"Irisin attenuates oxidative stress, mitochondrial dysfunction, and apoptosis in the H9C2 cellular model of septic cardiomyopathy through augmenting fundc1-dependent mitophagy","volume":"2021","author":"Jiang","year":"2021","journal-title":"Oxid. Med. Cell Longev."},{"key":"B24","doi-asserted-by":"publisher","first-page":"148","DOI":"10.1038\/cmi.2015.95","article-title":"Molecular mechanisms regulating NLRP3 inflammasome activation","volume":"13","author":"Jo","year":"2016","journal-title":"Cell Mol. Immunol."},{"key":"B25","doi-asserted-by":"publisher","first-page":"97","DOI":"10.1016\/j.chom.2018.05.009","article-title":"Lipid peroxidation drives gasdermin D-mediated pyroptosis in lethal polymicrobial sepsis","volume":"24","author":"Kang","year":"2018","journal-title":"Cell Host Microbe"},{"key":"B26","doi-asserted-by":"publisher","first-page":"168","DOI":"10.1016\/S0140-6736(19)33065-X","article-title":"A global accounting of sepsis","volume":"395","author":"Kempker","year":"2020","journal-title":"Lancet"},{"key":"B27","doi-asserted-by":"publisher","first-page":"673","DOI":"10.1016\/j.tcb.2017.05.005","article-title":"Gasdermins: Effectors of pyroptosis","volume":"27","author":"Kovacs","year":"2017","journal-title":"Trends Cell Biol."},{"key":"B28","doi-asserted-by":"publisher","first-page":"101215","DOI":"10.1016\/j.redox.2019.101215","article-title":"STING-IRF3 contributes to lipopolysaccharide-induced cardiac dysfunction, inflammation, apoptosis and pyroptosis by activating NLRP3","volume":"24","author":"Li","year":"2019","journal-title":"Redox Biol."},{"key":"B29","doi-asserted-by":"publisher","first-page":"59","DOI":"10.1186\/s12964-022-00877-5","article-title":"AIP1 suppresses neovascularization by inhibiting the NOX4-induced NLRP3\/NLRP6 imbalance in a murine corneal alkali burn model","volume":"20","author":"Li","year":"2022","journal-title":"Cell Commun. Signal"},{"key":"B30","doi-asserted-by":"publisher","first-page":"1009","DOI":"10.1097\/SHK.0000000000001775","article-title":"Irisin protects against LPS-stressed cardiac damage through inhibiting inflammation, apoptosis, and pyroptosis","volume":"56","author":"Li","year":"2021","journal-title":"Shock"},{"key":"B31","doi-asserted-by":"publisher","first-page":"12","DOI":"10.1186\/s13045-019-0841-3","article-title":"MiR-612 regulates invadopodia of hepatocellular carcinoma by HADHA-mediated lipid reprogramming","volume":"13","author":"Liu","year":"2020","journal-title":"J. Hematol. Oncol."},{"key":"B32","doi-asserted-by":"publisher","first-page":"1183","DOI":"10.1038\/cr.2015.124","article-title":"Gasdermin D: The long-awaited executioner of pyroptosis","volume":"25","author":"Man","year":"2015","journal-title":"Cell Res."},{"key":"B33","doi-asserted-by":"publisher","first-page":"1254","DOI":"10.1161\/CIRCRESAHA.116.302317","article-title":"Innate immunity and the failing heart: The cytokine hypothesis revisited","volume":"116","author":"Mann","year":"2015","journal-title":"Circ. Res."},{"key":"B34","doi-asserted-by":"publisher","first-page":"793","DOI":"10.1161\/CIRCULATIONAHA.106.678359","article-title":"Sepsis and the heart","volume":"116","author":"Merx","year":"2007","journal-title":"Circulation"},{"key":"B35","doi-asserted-by":"publisher","first-page":"4671","DOI":"10.1038\/s41467-019-12482-1","article-title":"TFPa\/HADHA is required for fatty acid beta-oxidation and cardiolipin re-modeling in human cardiomyocytes","volume":"10","author":"Miklas","year":"2019","journal-title":"Nat. Commun."},{"key":"B36","doi-asserted-by":"publisher","first-page":"286","DOI":"10.1038\/s41586-020-2576-2","article-title":"Dichotomous engagement of HDAC3 activity governs inflammatory responses","volume":"584","author":"Nguyen","year":"2020","journal-title":"Nature"},{"key":"B37","doi-asserted-by":"publisher","first-page":"84","DOI":"10.1016\/j.jacbts.2021.08.006","article-title":"Targeting the inflammasome in cardiovascular disease","volume":"7","author":"Olsen","year":"2022","journal-title":"JACC Basic Transl. Sci."},{"key":"B38","doi-asserted-by":"publisher","first-page":"1627","DOI":"10.1016\/j.bbadis.2019.03.015","article-title":"Mitochondrial ALDH2 protects against lipopolysaccharide-induced myocardial contractile dysfunction by suppression of ER stress and autophagy","volume":"1865","author":"Pang","year":"2019","journal-title":"Biochim. Biophys. Acta Mol. Basis Dis."},{"key":"B39","doi-asserted-by":"publisher","first-page":"4047","DOI":"10.3390\/ijms23074047","article-title":"Metabolic syndrome and beta-oxidation of long-chain fatty acids in the brain, heart, and kidney mitochondria","volume":"23","author":"Panov","year":"2022","journal-title":"Int. J. Mol. Sci."},{"key":"B40","doi-asserted-by":"publisher","first-page":"227","DOI":"10.7326\/0003-4819-113-3-227","article-title":"Septic shock in humans. Advances in the understanding of pathogenesis, cardiovascular dysfunction, and therapy","volume":"113","author":"Parrillo","year":"1990","journal-title":"Ann. Intern Med."},{"key":"B41","doi-asserted-by":"publisher","first-page":"620","DOI":"10.1016\/j.mayocp.2012.01.018","article-title":"Clinical spectrum, frequency, and significance of myocardial dysfunction in severe sepsis and septic shock","volume":"87","author":"Pulido","year":"2012","journal-title":"Mayo Clin. Proc."},{"key":"B42","doi-asserted-by":"publisher","first-page":"1141","DOI":"10.1161\/CIRCRESAHA.121.318908","article-title":"Deficient chaperone-mediated autophagy promotes inflammation and atherosclerosis","volume":"129","author":"Qiao","year":"2021","journal-title":"Circ. Res."},{"key":"B43","doi-asserted-by":"publisher","first-page":"792","DOI":"10.1016\/j.cell.2016.03.046","article-title":"Inflammasome complexes: Emerging mechanisms and effector functions","volume":"165","author":"Rathinam","year":"2016","journal-title":"Cell"},{"key":"B44","doi-asserted-by":"publisher","first-page":"eaat2738","DOI":"10.1126\/sciimmunol.aat2738","article-title":"Chemical disruption of the pyroptotic pore-forming protein gasdermin D inhibits inflammatory cell death and sepsis","volume":"3","author":"Rathkey","year":"2018","journal-title":"Sci. Immunol."},{"key":"B45","doi-asserted-by":"publisher","first-page":"200","DOI":"10.1016\/S0140-6736(19)32989-7","article-title":"Global, regional, and national sepsis incidence and mortality, 1990-2017: Analysis for the global burden of disease study","volume":"395","author":"Rudd","year":"2020","journal-title":"Lancet"},{"key":"B46","doi-asserted-by":"publisher","first-page":"245","DOI":"10.1016\/j.tibs.2016.10.004","article-title":"Pyroptosis: Gasdermin-Mediated programmed necrotic cell death","volume":"42","author":"Shi","year":"2017","journal-title":"Trends Biochem. Sci."},{"key":"B47","doi-asserted-by":"publisher","first-page":"233","DOI":"10.1186\/1756-0500-7-233","article-title":"A robust scoring system to evaluate sepsis severity in an animal model","volume":"7","author":"Shrum","year":"2014","journal-title":"BMC Res. Notes"},{"key":"B48","doi-asserted-by":"publisher","first-page":"801","DOI":"10.1001\/jama.2016.0287","article-title":"The third international consensus definitions for sepsis and septic shock (Sepsis-3)","volume":"315","author":"Singer","year":"2016","journal-title":"JAMA"},{"key":"B49","doi-asserted-by":"publisher","first-page":"9198","DOI":"10.1038\/s41598-020-66011-y","article-title":"A single dose of eHSP72 attenuates sepsis severity in mice","volume":"10","author":"Sulzbacher","year":"2020","journal-title":"Sci. Rep."},{"key":"B50","doi-asserted-by":"publisher","first-page":"477","DOI":"10.1038\/s41577-019-0165-0","article-title":"The NLRP3 inflammasome: Molecular activation and regulation to therapeutics","volume":"19","author":"Swanson","year":"2019","journal-title":"Nat. Rev. Immunol."},{"key":"B51","doi-asserted-by":"publisher","first-page":"172","DOI":"10.2119\/molmed.2010.00114","article-title":"Inhibition of aldehyde dehydrogenase 2 by oxidative stress is associated with cardiac dysfunction in diabetic rats","volume":"17","author":"Wang","year":"2011","journal-title":"Mol. Med."},{"key":"B52","doi-asserted-by":"publisher","first-page":"66","DOI":"10.1007\/s00395-020-00832-w","article-title":"PCSK9 regulates pyroptosis via mtDNA damage in chronic myocardial ischemia","volume":"115","author":"Wang","year":"2020","journal-title":"Basic Res. Cardiol."},{"key":"B53","doi-asserted-by":"publisher","first-page":"113199","DOI":"10.1016\/j.biopha.2022.113199","article-title":"Irisin attenuates sepsis-induced cardiac dysfunction by attenuating inflammation-induced pyroptosis through a mitochondrial ubiquitin ligase-dependent mechanism","volume":"152","author":"Xiong","year":"2022","journal-title":"Biomed. Pharmacother."},{"key":"B54","doi-asserted-by":"publisher","first-page":"60","DOI":"10.1016\/j.intimp.2019.01.025","article-title":"NADPH oxidase 2-mediated NLRP1 inflammasome activation involves in neuronal senescence in hippocampal neurons in vitro","volume":"69","author":"Xu","year":"2019","journal-title":"Int. Immunopharmacol."},{"key":"B55","doi-asserted-by":"publisher","first-page":"1035","DOI":"10.1016\/j.it.2019.09.005","article-title":"Emerging activators and regulators of inflammasomes and pyroptosis","volume":"40","author":"Xue","year":"2019","journal-title":"Trends Immunol."},{"key":"B56","doi-asserted-by":"publisher","first-page":"1538","DOI":"10.1093\/cvr\/cvx130","article-title":"Insights into innate immune signalling in controlling cardiac remodelling","volume":"113","author":"Zhang","year":"2017","journal-title":"Cardiovasc Res."},{"key":"B57","doi-asserted-by":"publisher","first-page":"674","DOI":"10.1016\/j.cell.2020.03.040","article-title":"Caspase-6 is a key regulator of innate immunity, inflammasome activation, and host defense","volume":"181","author":"Zheng","year":"2020","journal-title":"Cell"},{"key":"B58","doi-asserted-by":"publisher","first-page":"252","DOI":"10.1172\/JCI122064","article-title":"Acetaldehyde dehydrogenase 2 interactions with LDLR and AMPK regulate foam cell formation","volume":"129","author":"Zhong","year":"2019","journal-title":"J. Clin. Invest."},{"key":"B59","doi-asserted-by":"publisher","first-page":"198","DOI":"10.1038\/s41586-018-0372-z","article-title":"New mitochondrial DNA synthesis enables NLRP3 inflammasome activation","volume":"560","author":"Zhong","year":"2018","journal-title":"Nature"},{"key":"B60","doi-asserted-by":"publisher","first-page":"896","DOI":"10.1016\/j.cell.2015.12.057","article-title":"NF-\u03baB restricts inflammasome activation via elimination of damaged mitochondria","volume":"164","author":"Zhong","year":"2016","journal-title":"Cell"},{"key":"B61","doi-asserted-by":"publisher","first-page":"221","DOI":"10.1038\/nature09663","article-title":"A role for mitochondria in NLRP3 inflammasome activation","volume":"469","author":"Zhou","year":"2011","journal-title":"Nature"}],"container-title":["Frontiers in Pharmacology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fphar.2023.1125866\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,3,13]],"date-time":"2023-03-13T05:23:28Z","timestamp":1678685008000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fphar.2023.1125866\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,3,13]]},"references-count":61,"alternative-id":["10.3389\/fphar.2023.1125866"],"URL":"https:\/\/doi.org\/10.3389\/fphar.2023.1125866","relation":{},"ISSN":["1663-9812"],"issn-type":[{"value":"1663-9812","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,3,13]]},"article-number":"1125866"}}