{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,9]],"date-time":"2026-10-09T21:39:29Z","timestamp":1791581969602,"version":"4.3.4"},"reference-count":71,"publisher":"MDPI AG","issue":"2","license":[{"start":{"date-parts":[[2022,1,19]],"date-time":"2022-01-19T00:00:00Z","timestamp":1642550400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"National Institute of Health","award":["R01 HL144478"],"award-info":[{"award-number":["R01 HL144478"]}]},{"DOI":"10.13039\/100000738","name":"United States Department of Veterans Affairs","doi-asserted-by":"publisher","award":["5I01BX001786"],"award-info":[{"award-number":["5I01BX001786"]}],"id":[{"id":"10.13039\/100000738","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Pathogens"],"abstract":"<jats:p>The innate immune response to P. aeruginosa pulmonary infections relies on a network of pattern recognition receptors, including intracellular inflammasome complexes, which can recognize both pathogen- and host-derived signals and subsequently promote downstream inflammatory signaling. Current evidence suggests that the inflammasome does not contribute to bacterial clearance and, in fact, that dysregulated inflammasome activation is harmful in acute and chronic P. aeruginosa lung infection. Given the role of mitochondrial damage signals in recruiting inflammasome signaling, we investigated whether mitochondrial-targeted therapies could attenuate inflammasome signaling in response to P. aeruginosa and decrease pathogenicity of infection. In particular, we investigated the small molecule, ZLN005, which transcriptionally activates peroxisome proliferator-activated receptor-\u03b3 coactivator-1\u03b1 (PGC-1\u03b1), a master regulator of mitochondrial biogenesis, antioxidant defense, and cellular respiration. We demonstrate that P. aeruginosa infection promotes the expression of inflammasome components and attenuates several components of mitochondrial repair pathways in vitro in lung epithelial cells and in vivo in an acute pneumonia model. ZLN005 activates PGC-1\u03b1 and its downstream effector, Sirtuin 3 (SIRT3), a mitochondrial-localized deacetylase important for cellular metabolic processes and for reactive oxygen species homeostasis. ZLN005 also attenuates inflammasome signaling induced by P. aeruginosa in bronchial epithelial cells and this action is dependent on ZLN005 activation of SIRT3. ZLN005 treatment reduces epithelial-barrier dysfunction caused by P. aeruginosa and decreases pathogenicity in an in vivo pneumonia model. Therapies that activate the PGC-1\u03b1\u2014SIRT3 axis may provide a complementary approach in the treatment of P. aeruginosa infection.<\/jats:p>","DOI":"10.3390\/pathogens11020116","type":"journal-article","created":{"date-parts":[[2022,1,19]],"date-time":"2022-01-19T21:01:51Z","timestamp":1642626111000},"page":"116","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":13,"title":["The Effect of PGC-1alpha-SIRT3 Pathway Activation on Pseudomonas aeruginosa Infection"],"prefix":"10.3390","volume":"11","author":[{"given":"Nicholas M.","family":"Maurice","sequence":"first","affiliation":[{"name":"Department of Medicine, Division of Pulmonary, Allergy, Critical Care, and Sleep Medicine, Emory University School of Medicine, Atlanta, GA 30322, USA"},{"name":"Atlanta Veterans Affairs Health Care System, Decatur, GA 30033, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Brahmchetna","family":"Bedi","sequence":"additional","affiliation":[{"name":"Department of Medicine, Division of Pulmonary, Allergy, Critical Care, and Sleep Medicine, Emory University School of Medicine, Atlanta, GA 30322, USA"},{"name":"Atlanta Veterans Affairs Health Care System, Decatur, GA 30033, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhihong","family":"Yuan","sequence":"additional","affiliation":[{"name":"VA Nebraska Western Iowa Health Care System, Omaha, NE 68105, USA"},{"name":"Division of Pulmonary, Critical Care & Sleep, Department of Internal Medicine, University of Nebraska Medical Center, Omaha, NE 68198, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kuo-Chuan","family":"Lin","sequence":"additional","affiliation":[{"name":"Department of Medicine, Division of Pulmonary, Allergy, Critical Care, and Sleep Medicine, Emory University School of Medicine, Atlanta, GA 30322, USA"},{"name":"Atlanta Veterans Affairs Health Care System, Decatur, GA 30033, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joanna B.","family":"Goldberg","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Division of Pulmonology, Allergy\/Immunology, Cystic Fibrosis, and Sleep, Emory University, Atlanta, GA 30322, USA"},{"name":"Children\u2019s Healthcare of Atlanta, Center for CF and Airways Disease Research, Atlanta, GA 30322, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"C. Michael","family":"Hart","sequence":"additional","affiliation":[{"name":"Department of Medicine, Division of Pulmonary, Allergy, Critical Care, and Sleep Medicine, Emory University School of Medicine, Atlanta, GA 30322, USA"},{"name":"Atlanta Veterans Affairs Health Care System, Decatur, GA 30033, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kristina L.","family":"Bailey","sequence":"additional","affiliation":[{"name":"VA Nebraska Western Iowa Health Care System, Omaha, NE 68105, USA"},{"name":"Division of Pulmonary, Critical Care & Sleep, Department of Internal Medicine, University of Nebraska Medical Center, Omaha, NE 68198, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ruxana T.","family":"Sadikot","sequence":"additional","affiliation":[{"name":"VA Nebraska Western Iowa Health Care System, Omaha, NE 68105, USA"},{"name":"Division of Pulmonary, Critical Care & Sleep, Department of Internal Medicine, University of Nebraska Medical Center, Omaha, NE 68198, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,1,19]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1209","DOI":"10.1164\/rccm.200408-1044SO","article-title":"Pathogen-host interactions in Pseudomonas aeruginosa pneumonia","volume":"171","author":"Sadikot","year":"2005","journal-title":"Am. J. Respir. Crit. Care Med."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"428","DOI":"10.1165\/rcmb.2017-0321TR","article-title":"Pseudomonas aeruginosa Biofilms: Host Response and Clinical Implications in Lung Infections","volume":"58","author":"Maurice","year":"2018","journal-title":"Am. J. Respir. Cell Mol. Biol."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"L627","DOI":"10.1152\/ajplung.00225.2012","article-title":"The inflammasome in lung diseases","volume":"303","author":"Kutuzov","year":"2012","journal-title":"Am. J. Physiol. Lung Cell. Mol. Physiol."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"1133","DOI":"10.1016\/j.micinf.2011.07.011","article-title":"Innate immune responses to Pseudomonas aeruginosa infection","volume":"13","author":"Lavoie","year":"2011","journal-title":"Microbes Infect."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"125","DOI":"10.1016\/j.coi.2020.11.006","article-title":"Inflammasome activation and evasion by bacterial pathogens","volume":"68","author":"Ta","year":"2021","journal-title":"Curr. Opin. Immunol."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"354","DOI":"10.1038\/ni777","article-title":"Human Toll-like receptor 4 recognizes host-specific LPS modifications","volume":"3","author":"Hajjar","year":"2002","journal-title":"Nat. Immunol."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"1246","DOI":"10.1126\/science.1240248","article-title":"Noncanonical inflammasome activation by intracellular LPS independent of TLR4","volume":"341","author":"Kayagaki","year":"2013","journal-title":"Science"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"596","DOI":"10.1038\/nature10510","article-title":"The NLRC4 inflammasome receptors for bacterial flagellin and type III secretion apparatus","volume":"477","author":"Zhao","year":"2011","journal-title":"Nature"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"5623","DOI":"10.4049\/jimmunol.1200195","article-title":"NLRC4 inflammasome-mediated production of IL-1\u03b2 modulates mucosal immunity in the lung against gram-negative bacterial infection","volume":"188","author":"Cai","year":"2012","journal-title":"J. Immunol."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"449","DOI":"10.1038\/ni.2263","article-title":"NLRC4-driven production of IL-1\u03b2 discriminates between pathogenic and commensal bacteria and promotes host intestinal defense","volume":"13","author":"Franchi","year":"2012","journal-title":"Nat. Immunol."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"3076","DOI":"10.1073\/pnas.0913087107","article-title":"Innate immune detection of the type III secretion apparatus through the NLRC4 inflammasome","volume":"107","author":"Miao","year":"2010","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"3822","DOI":"10.1128\/IAI.00433-10","article-title":"Naturally produced outer membrane vesicles from Pseudomonas aeruginosa elicit a potent innate immune response via combined sensing of both lipopolysaccharide and protein components","volume":"78","author":"Ellis","year":"2010","journal-title":"Infect. Immun."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"581165","DOI":"10.3389\/fimmu.2020.581165","article-title":"Bacterial Outer Membrane Vesicle-Mediated Cytosolic Delivery of Flagellin Triggers Host NLRC4 Canonical Inflammasome Signaling","volume":"11","author":"Yang","year":"2020","journal-title":"Front. Immunol."},{"key":"ref_14","doi-asserted-by":"crossref","unstructured":"McHugh, B.J., Wang, R., Li, H.N., Beaumont, P.E., Kells, R., Stevens, H., Young, L., Rossi, A.G., Gray, R.D., and Dorin, J.R. (2019). Cathelicidin is a \u201cfire alarm\u201d, generating protective NLRP3-dependent airway epithelial cell inflammatory responses during infection with Pseudomonas aeruginosa. PLoS Pathog., 15.","DOI":"10.1371\/journal.ppat.1007694"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"6201","DOI":"10.1038\/ncomms7201","article-title":"Mitochondrial Ca2+-dependent NLRP3 activation exacerbates the Pseudomonas aeruginosa-driven inflammatory response in cystic fibrosis","volume":"6","author":"Rimessi","year":"2015","journal-title":"Nat. Commun."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"166","DOI":"10.4161\/15548627.2014.981915","article-title":"Mitochondrial damage contributes to Pseudomonas aeruginosa activation of the inflammasome and is downregulated by autophagy","volume":"11","author":"Jabir","year":"2015","journal-title":"Autophagy"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"1418","DOI":"10.1038\/s41564-020-0773-2","article-title":"Mitochondrial dysfunction caused by outer membrane vesicles from Gram-negative bacteria activates intrinsic apoptosis and inflammation","volume":"5","author":"Deo","year":"2020","journal-title":"Nat. Microbiol."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"L285","DOI":"10.1152\/ajplung.00461.2000","article-title":"Role of interleukin-1 in the pulmonary immune response during Pseudomonas aeruginosa pneumonia","volume":"282","author":"Schultz","year":"2002","journal-title":"Am. J. Physiol. Lung Cell. Mol. Physiol."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"1630","DOI":"10.1128\/IAI.71.4.1630-1634.2003","article-title":"Interleukin-18 impairs the pulmonary host response to Pseudomonas aeruginosa","volume":"71","author":"Schultz","year":"2003","journal-title":"Infect. Immun."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"1630","DOI":"10.1172\/JCI66142","article-title":"Activation of inflammasome signaling mediates pathology of acute P. aeruginosa pneumonia","volume":"123","author":"Cohen","year":"2013","journal-title":"J. Clin. Investig."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"e13251","DOI":"10.1111\/cmi.13251","article-title":"Inflammasome activation by Pseudomonas aeruginosa\u2019s ExlA pore-forming toxin is detrimental for the host","volume":"22","author":"Bouillot","year":"2020","journal-title":"Cell. Microbiol."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"1381","DOI":"10.1164\/rccm.201905-1013OC","article-title":"Specific Inhibition of the NLRP3 Inflammasome as an Antiinflammatory Strategy in Cystic Fibrosis","volume":"200","author":"McElvaney","year":"2019","journal-title":"Am. J. Respir. Crit. Care Med."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"10791","DOI":"10.1038\/ncomms10791","article-title":"IL-1 receptor antagonist ameliorates inflammasome-dependent inflammation in murine and human cystic fibrosis","volume":"7","author":"Iannitti","year":"2016","journal-title":"Nat. Commun."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"11929","DOI":"10.1038\/s41598-019-47457-1","article-title":"Pseudomonas aeruginosa Induced Host Epithelial Cell Mitochondrial Dysfunction","volume":"9","author":"Maurice","year":"2019","journal-title":"Sci. Rep."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"1297","DOI":"10.2337\/db12-0703","article-title":"Novel small-molecule PGC-1\u03b1 transcriptional regulator with beneficial effects on diabetic db\/db mice","volume":"62","author":"Zhang","year":"2013","journal-title":"Diabetes"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"250","DOI":"10.1159\/000455857","article-title":"Inflammation: A Double-Edged Sword in the Response to Pseudomonas aeruginosa Infection","volume":"9","author":"Lin","year":"2017","journal-title":"J. Innate Immun."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"442","DOI":"10.1159\/000487515","article-title":"Pseudomonas aeruginosa and Klebsiella pneumoniae Adaptation to Innate Immune Clearance Mechanisms in the Lung","volume":"10","author":"Riquelme","year":"2018","journal-title":"J. Innate Immun."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"809","DOI":"10.1172\/JCI81113","article-title":"Mitochondria in lung disease","volume":"126","author":"Cloonan","year":"2016","journal-title":"J. Clin. Investig."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"2","DOI":"10.3389\/fcvm.2020.00002","article-title":"Multiple Levels of PGC-1\u03b1 Dysregulation in Heart Failure","volume":"7","author":"Oka","year":"2020","journal-title":"Front. Cardiovasc. Med."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"33","DOI":"10.1016\/j.bbrc.2015.08.092","article-title":"GLP-1 contributes to increases in PGC-1\u03b1 expression by downregulating miR-23a to reduce apoptosis","volume":"466","author":"Wang","year":"2015","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.yjmcc.2014.06.012","article-title":"MicroRNA-23a mediates mitochondrial compromise in estrogen deficiency-induced concentric remodeling via targeting PGC-1\u03b1","volume":"75","author":"Sun","year":"2014","journal-title":"J. Mol. Cell. Cardiol."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"186","DOI":"10.1002\/hep.25632","article-title":"Stat3-mediated activation of microRNA-23a suppresses gluconeogenesis in hepatocellular carcinoma by down-regulating glucose-6-phosphatase and peroxisome proliferator-activated receptor gamma, coactivator 1 alpha","volume":"56","author":"Wang","year":"2012","journal-title":"Hepatology"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"73","DOI":"10.1016\/j.taap.2019.02.016","article-title":"Inhibition of miR-23a attenuates doxorubicin-induced mitochondria-dependent cardiomyocyte apoptosis by targeting the PGC-1\u03b1\/Drp1 pathway","volume":"369","author":"Du","year":"2019","journal-title":"Toxicol. Appl. Pharmacol."},{"key":"ref_34","doi-asserted-by":"crossref","unstructured":"Kong, X., Wang, R., Xue, Y., Liu, X., Zhang, H., Chen, Y., Fang, F., and Chang, Y. (2010). Sirtuin 3, a new target of PGC-1\u03b1, plays an important role in the suppression of ROS and mitochondrial biogenesis. PLoS ONE, 5.","DOI":"10.1371\/journal.pone.0011707"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"16958","DOI":"10.1074\/jbc.M110.202390","article-title":"Peroxisome proliferator-activated receptor-\u03b3 coactivator-1\u03b1 controls transcription of the Sirt3 gene, an essential component of the thermogenic brown adipocyte phenotype","volume":"286","author":"Giralt","year":"2011","journal-title":"J. Biol. Chem."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"151","DOI":"10.1165\/rcmb.2015-0231TR","article-title":"Regulation and Function of the Nucleotide Binding Domain Leucine-Rich Repeat-Containing Receptor, Pyrin Domain-Containing-3 Inflammasome in Lung Disease","volume":"54","author":"Lee","year":"2016","journal-title":"Am. J. Respir. Cell Mol. Biol."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"617","DOI":"10.1083\/jcb.201602089","article-title":"The cell biology of inflammasomes: Mechanisms of inflammasome activation and regulation","volume":"213","author":"Sharma","year":"2016","journal-title":"J. Cell Biol."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"787","DOI":"10.4049\/jimmunol.0901363","article-title":"Cutting edge: NF-\u03baB activating pattern recognition and cytokine receptors license NLRP3 inflammasome activation by regulating NLRP3 expression","volume":"183","author":"Bauernfeind","year":"2009","journal-title":"J. Immunol."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"3651","DOI":"10.1172\/JCI120845","article-title":"Mitochondrial fidelity and metabolic agility control immune cell fate and function","volume":"128","author":"Sack","year":"2018","journal-title":"J. Clin. Investig."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"613","DOI":"10.4049\/jimmunol.1100613","article-title":"Cutting edge: Reactive oxygen species inhibitors block priming, but not activation, of the NLRP3 inflammasome","volume":"187","author":"Bauernfeind","year":"2011","journal-title":"J. Immunol."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"27425","DOI":"10.1074\/jbc.M115.667063","article-title":"Rotenone-induced Impairment of Mitochondrial Electron Transport Chain Confers a Selective Priming Signal for NLRP3 Inflammasome Activation","volume":"290","author":"Won","year":"2015","journal-title":"J. Biol. Chem."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"488","DOI":"10.1038\/ni.3704","article-title":"Mitochondria are the powerhouses of immunity","volume":"18","author":"Mills","year":"2017","journal-title":"Nat. Immunol."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"495","DOI":"10.1146\/annurev-physiol-022516-034322","article-title":"Mitochondrial Dysfunction in Lung Pathogenesis","volume":"79","author":"Piantadosi","year":"2017","journal-title":"Annu. Rev. Physiol."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"265","DOI":"10.1146\/annurev-cellbio-021820-101354","article-title":"Mitochondrial Quality Control and Restraining Innate Immunity","volume":"36","author":"Moehlman","year":"2020","journal-title":"Annu. Rev. Cell Dev. Biol."},{"key":"ref_45","doi-asserted-by":"crossref","unstructured":"Picca, A., Lezza, A.M.S., Leeuwenburgh, C., Pesce, V., Calvani, R., Landi, F., Bernabei, R., and Marzetti, E. (2017). Fueling Inflamm-Aging through Mitochondrial Dysfunction: Mechanisms and Molecular Targets. Int. J. Mol. Sci., 18.","DOI":"10.3390\/ijms18050933"},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"648","DOI":"10.1165\/rcmb.2016-0293OC","article-title":"PPAR\u03b3 Regulates Mitochondrial Structure and Function and Human Pulmonary Artery Smooth Muscle Cell Proliferation","volume":"58","author":"Yeligar","year":"2018","journal-title":"Am. J. Respir. Cell Mol. Biol."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"89","DOI":"10.1016\/j.freeradbiomed.2020.03.031","article-title":"Oroxylin a promotes PGC-1\u03b1\/Mfn2 signaling to attenuate hepatocyte pyroptosis via blocking mitochondrial ROS in alcoholic liver disease","volume":"153","author":"Kai","year":"2020","journal-title":"Free Radic. Biol. Med."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"138","DOI":"10.1097\/SHK.0000000000000075","article-title":"Burn plus lipopolysaccharide augments endoplasmic reticulum stress and NLRP3 inflammasome activation and reduces PGC-1\u03b1 in liver","volume":"41","author":"Diao","year":"2014","journal-title":"Shock"},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"965","DOI":"10.1089\/ars.2014.6200","article-title":"Regulation of mitochondrial biogenesis and its intersection with inflammatory responses","volume":"22","author":"Cherry","year":"2015","journal-title":"Antioxid. Redox Signal."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"152720","DOI":"10.1016\/j.tox.2021.152720","article-title":"NLRP3 inflammasome mediated pyroptosis is involved in cadmium exposure-induced neuroinflammation through the IL-1\u03b2\/IkB-\u03b1-NF-\u03baB-NLRP3 feedback loop in swine","volume":"453","author":"Cai","year":"2021","journal-title":"Toxicology"},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"700","DOI":"10.1016\/j.ijcard.2016.06.236","article-title":"SIRT3 in cardiovascular diseases: Emerging roles and therapeutic implications","volume":"220","author":"Lu","year":"2016","journal-title":"Int. J. Cardiol."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"13653","DOI":"10.1073\/pnas.222538099","article-title":"SIRT3, a human SIR2 homologue, is an NAD-dependent deacetylase localized to mitochondria","volume":"99","author":"Onyango","year":"2002","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"634","DOI":"10.1016\/j.exger.2012.08.007","article-title":"SIRT3 regulation of mitochondrial oxidative stress","volume":"48","author":"Bause","year":"2013","journal-title":"Exp. Gerontol."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"L68","DOI":"10.1152\/ajplung.00188.2016","article-title":"SIRT3 blocks myofibroblast differentiation and pulmonary fibrosis by preventing mitochondrial DNA damage","volume":"312","author":"Bindu","year":"2017","journal-title":"Am. J. Physiol. Lung Cell. Mol. Physiol."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"715","DOI":"10.1172\/JCI77632","article-title":"Sirtuin 3-dependent mitochondrial dynamic improvements protect against acute kidney injury","volume":"125","author":"Morigi","year":"2015","journal-title":"J. Clin. Investig."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"414","DOI":"10.3389\/fnins.2018.00414","article-title":"Sirt3 Ameliorates Oxidative Stress and Mitochondrial Dysfunction after Intracerebral Hemorrhage in Diabetic Rats","volume":"12","author":"Zheng","year":"2018","journal-title":"Front. Neurosci."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"33201","DOI":"10.1038\/srep33201","article-title":"Protective effects of sirtuin 3 in a murine model of sepsis-induced acute kidney injury","volume":"6","author":"Zhao","year":"2016","journal-title":"Sci. Rep."},{"key":"ref_58","first-page":"1","article-title":"Inhibition of microRNA-297 alleviates THLE-2 cell injury induced by hypoxia\/reoxygenation by inhibiting NLRP3 inflammasome activation via SIRT3","volume":"24","author":"Yue","year":"2021","journal-title":"Can. J. Physiol. Pharmacol."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"17547","DOI":"10.1038\/s41598-018-35890-7","article-title":"SIRT3 deficiency-induced mitochondrial dysfunction and inflammasome formation in the brain","volume":"8","author":"Tyagi","year":"2018","journal-title":"Sci. Rep."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"4592","DOI":"10.1172\/JCI83260","article-title":"Fasting and refeeding differentially regulate NLRP3 inflammasome activation in human subjects","volume":"125","author":"Traba","year":"2015","journal-title":"J. Clin. Investig."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"12153","DOI":"10.1074\/jbc.M117.791715","article-title":"Prolonged fasting suppresses mitochondrial NLRP3 inflammasome assembly and activation via SIRT3-mediated activation of superoxide dismutase 2","volume":"292","author":"Traba","year":"2017","journal-title":"J. Biol. Chem."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"230","DOI":"10.1038\/s41401-020-0490-7","article-title":"Sirtuin 3 deficiency exacerbates diabetic cardiomyopathy via necroptosis enhancement and NLRP3 activation","volume":"42","author":"Song","year":"2021","journal-title":"Acta Pharmacol. Sin."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"e312","DOI":"10.1002\/ctm2.312","article-title":"Vitamin D3 ameliorates nitrogen mustard-induced cutaneous inflammation by inactivating the NLRP3 inflammasome through the SIRT3-SOD2-mtROS signaling pathway","volume":"11","author":"Dong","year":"2021","journal-title":"Clin. Transl. Med."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"114665","DOI":"10.1016\/j.bcp.2021.114665","article-title":"Protective role of sirtuin3 against oxidative stress and NLRP3 inflammasome in cholesterol accumulation and foam cell formation of macrophages with ox-LDL-stimulation","volume":"192","author":"Ding","year":"2021","journal-title":"Biochem. Pharmacol."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"e006347","DOI":"10.1161\/JAHA.117.006347","article-title":"Trimethylamine-N-Oxide Induces Vascular Inflammation by Activating the NLRP3 Inflammasome Through the SIRT3-SOD2-mtROS Signaling Pathway","volume":"6","author":"Chen","year":"2017","journal-title":"J. Am. Heart Assoc."},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"764","DOI":"10.1016\/j.bbadis.2017.12.027","article-title":"Sirtuin 3-induced macrophage autophagy in regulating NLRP3 inflammasome activation","volume":"1864","author":"Liu","year":"2018","journal-title":"Biochim. Biophys. Acta. Mol. Basis Dis."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"3853","DOI":"10.1038\/s41598-017-04263-x","article-title":"Sirtuin 3 deficiency does not alter host defenses against bacterial and fungal infections","volume":"7","author":"Ciarlo","year":"2017","journal-title":"Sci. Rep."},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"1277","DOI":"10.1111\/j.1530-0277.2011.01463.x","article-title":"Alcohol decreases RhoA activity through a nitric oxide (NO)\/cyclic GMP(cGMP)\/protein kinase G (PKG)-dependent pathway in the airway epithelium","volume":"35","author":"Bailey","year":"2011","journal-title":"Alcohol. Clin. Exp. Res."},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"1001","DOI":"10.1002\/eji.200636636","article-title":"Bacterial clearance of Pseudomonas aeruginosa is enhanced by the inhibition of COX-2","volume":"37","author":"Sadikot","year":"2007","journal-title":"Eur. J. Immunol."},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"1975","DOI":"10.1128\/IAI.00164-16","article-title":"Enhanced Clearance of Pseudomonas aeruginosa by Peroxisome Proliferator-Activated Receptor Gamma","volume":"84","author":"Bedi","year":"2016","journal-title":"Infect. Immun."},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"3608","DOI":"10.1096\/fj.201700075R","article-title":"Peroxisome proliferator-activated receptor-\u03b3 agonists attenuate biofilm formation by Pseudomonas aeruginosa","volume":"31","author":"Bedi","year":"2017","journal-title":"FASEB J."}],"container-title":["Pathogens"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2076-0817\/11\/2\/116\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T22:04:12Z","timestamp":1760133852000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2076-0817\/11\/2\/116"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,1,19]]},"references-count":71,"journal-issue":{"issue":"2","published-online":{"date-parts":[[2022,2]]}},"alternative-id":["pathogens11020116"],"URL":"https:\/\/doi.org\/10.3390\/pathogens11020116","relation":{},"ISSN":["2076-0817"],"issn-type":[{"value":"2076-0817","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,1,19]]}}}