{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T05:01:29Z","timestamp":1790744489372,"version":"4.1.0"},"reference-count":105,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T00:00:00Z","timestamp":1790726400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100009103","name":"Education Department of Shaanxi Province","doi-asserted-by":"publisher","award":["24JR051"],"award-info":[{"award-number":["24JR051"]}],"id":[{"id":"10.13039\/501100009103","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Pharmacol."],"abstract":"<jats:p>Sepsis-associated acute lung injury (SALI) is characterised by mitochondrial oxidative stress, bioenergetic dysfunction, dysregulated inflammation, and disruption of the alveolar\u2013capillary barrier. MitoQ is a mitochondria-targeted redox modulator with experimental evidence of mitochondrial and pulmonary protection, making it a candidate strategy for limiting oxidative injury in SALI. This critical narrative review evaluates the redox pharmacology of MitoQ, direct pulmonary and sepsis-related evidence, mechanistic links between mitochondrial damage and innate immune signalling, and the major requirements for clinical translation. Available studies show that MitoQ reduces mitochondrial reactive oxygen species and lipid peroxidation, preserves membrane potential and ATP production, and attenuates epithelial, endothelial, and alveolar\u2013capillary barrier injury. Mechanistic studies further support links among mitochondrial dysfunction, abnormal mitochondrial DNA exposure, cGAS\u2013STING signalling, NLRP3\u2013GSDMD activation, pyroptosis, and pulmonary barrier failure. However, these downstream pathways have not yet been causally linked to MitoQ treatment in infection-associated SALI, and pulmonary or intramitochondrial drug exposure remains poorly defined. Human studies demonstrate oral feasibility and systemic redox pharmacodynamic activity but have not established pulmonary target engagement or clinical efficacy. Current evidence therefore supports MitoQ primarily as an upstream mitochondrial redox modulator with potential to preserve alveolar\u2013capillary function. Future studies should prioritise post-onset treatment, pulmonary and mitochondrial target engagement, pathway-specific causal validation, and assessment of host defence to determine its translational potential in SALI.<\/jats:p>","DOI":"10.3389\/fphar.2026.1975929","type":"journal-article","created":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T04:54:07Z","timestamp":1790744047000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["MitoQ in sepsis-associated acute lung injury: redox pharmacology, mechanistic evidence, and translational perspectives"],"prefix":"10.3389","volume":"17","author":[{"given":"Jiajia","family":"Yu","sequence":"first","affiliation":[{"name":"Department of Pharmacology, Shaanxi University of Chinese Medicine","place":["Xianyang, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuyu","family":"An","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, Shaanxi University of Chinese Medicine","place":["Xianyang, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yanni","family":"Mi","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, Shaanxi University of Chinese Medicine","place":["Xianyang, China"]},{"name":"Key Laboratory of Pharmacodynamic Mechanism and Material Basis of Traditional Chinese Medicine, Shaanxi Administration of Traditional Chinese Medicine","place":["Xianyang, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guoquan","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, Shaanxi University of Chinese Medicine","place":["Xianyang, China"]},{"name":"Key Laboratory of Pharmacodynamic Mechanism and Material Basis of Traditional Chinese Medicine, Shaanxi Administration of Traditional Chinese Medicine","place":["Xianyang, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bin","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, Shaanxi University of Chinese Medicine","place":["Xianyang, China"]},{"name":"Key Laboratory of Pharmacodynamic Mechanism and Material Basis of Traditional Chinese Medicine, Shaanxi Administration of Traditional Chinese Medicine","place":["Xianyang, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiping","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, Shaanxi University of Chinese Medicine","place":["Xianyang, China"]},{"name":"Key Laboratory of Pharmacodynamic Mechanism and Material Basis of Traditional Chinese Medicine, Shaanxi Administration of Traditional Chinese Medicine","place":["Xianyang, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,9,30]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"261","DOI":"10.1016\/j.it.2017.01.003","article-title":"Recent insights into the molecular mechanisms underlying pyroptosis and gasdermin family functions","volume":"38","author":"Aglietti","year":"2017","journal-title":"Trends Immunol."},{"key":"B2","doi-asserted-by":"publisher","first-page":"e196290","DOI":"10.1172\/jci196290","article-title":"Longitudinal multiomic signatures of ARDS and sepsis inflammatory phenotypes identify pathways associated with mortality","volume":"136","author":"Alipanah-Lechner","year":"2026","journal-title":"J. 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