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Nitrite ([Formula: see text]), which is reduced in vivo to form nitric oxide (NO), has recently emerged as an intrinsic signaling molecule with a prominent role in cytoprotection against I\/R injury. Using a murine model, we provide the evidence that nitrite mitigated I\/R-induced injury by diminishing infiltration of immune cells in the alveolar space, reducing pulmonary edema, and improving pulmonary function. Ultrastructural studies support severe mitochondrial impairment in the lung undergoing I\/R injury, which was significantly protected by nitrite treatment. Nitrite also abrogated the increased pulmonary vascular permeability caused by I\/R. In vitro, hypoxia-reoxygenation (H\/R) exacerbated cell death in lung epithelial and microvascular endothelial cells. This contributed to mitochondrial dysfunction as characterized by diminished complex I activity and mitochondrial membrane potential but increased mitochondrial reactive oxygen species (mtROS). Pretreatment of cells with nitrite robustly attenuated mtROS production through modulation of complex I activity. These findings illustrate a potential novel mechanism in which nitrite protects the lung against I\/R injury by regulating mitochondrial bioenergetics and vascular permeability. <\/jats:p>","DOI":"10.1152\/ajplung.00367.2018","type":"journal-article","created":{"date-parts":[[2020,2,19]],"date-time":"2020-02-19T20:55:44Z","timestamp":1582145744000},"page":"L580-L591","source":"Crossref","is-referenced-by-count":15,"title":["Nitrite attenuates mitochondrial impairment and vascular permeability induced by ischemia-reperfusion injury in the lung"],"prefix":"10.1152","volume":"318","author":[{"given":"Ajay","family":"Kumar","sequence":"first","affiliation":[{"name":"Division of Lung Transplantation and Lung Failure, Department of Cardiothoracic Surgery, University of Pittsburgh, Pittsburgh, Pennsylvania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8921-1944","authenticated-orcid":false,"given":"Kentaro","family":"Noda","sequence":"additional","affiliation":[{"name":"Division of Lung Transplantation and Lung Failure, Department of Cardiothoracic Surgery, University of Pittsburgh, Pittsburgh, Pennsylvania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Brian","family":"Philips","sequence":"additional","affiliation":[{"name":"Division of Lung Transplantation and Lung Failure, Department of Cardiothoracic Surgery, University of Pittsburgh, Pittsburgh, Pennsylvania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Murugesan","family":"Velayutham","sequence":"additional","affiliation":[{"name":"Vascular Medicine Institute, University of Pittsburgh, Pittsburgh, Pennsylvania"},{"name":"Thomas E. 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