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The mechanism(s) by which cell death is triggered remains incompletely defined, as does the impact of <jats:italic>Ft<\/jats:italic> on mitochondria, the host cell\u2019s organellar \u2018canary in a coal mine\u2019. Herein, we reveal that <jats:italic>Ft<\/jats:italic> infection of host cells, particularly macrophages and polymorphonuclear leukocytes, drives necroptosis via a receptor-interacting protein kinase 1\/3-mediated mechanism. During necroptosis mitochondria and other organelles become damaged. <jats:italic>Ft<\/jats:italic>-induced mitochondrial damage is characterized by: (i) a decrease in membrane potential and consequent mitochondrial oncosis or swelling, (ii) increased generation of superoxide radicals, and (iii) release of intact or damaged mitochondria into the lung parenchyma. Host cell recognition of and response to released mitochondria and other damage-associated molecular patterns engenders a sepsis-like syndrome typified by production of TNF, IL-1<jats:italic>\u03b2<\/jats:italic>, IL-6, IL-12p70, and IFN-<jats:italic>\u03b3<\/jats:italic> during late-phase tularemia (\u2a7e72\u2009h), but are absent early during infection.<\/jats:p>","DOI":"10.1038\/cddiscovery.2017.56","type":"journal-article","created":{"date-parts":[[2017,9,25]],"date-time":"2017-09-25T10:56:09Z","timestamp":1506336969000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":13,"title":["Necroptotic debris including damaged mitochondria elicits sepsis-like syndrome during late-phase tularemia"],"prefix":"10.1038","volume":"3","author":[{"given":"Anju","family":"Singh","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sivakumar","family":"Periasamy","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Meenakshi","family":"Malik","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chandra Shekhar","family":"Bakshi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laurie","family":"Stephen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jeffrey G","family":"Ault","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carmen A","family":"Mannella","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Timothy J","family":"Sellati","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2017,9,25]]},"reference":[{"key":"BFcddiscovery201756_CR1","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1111\/j.1574-6968.2009.01791.x","volume":"301","author":"MJ Parmely","year":"2009","unstructured":"Parmely MJ, Fischer JL, Pinson DM . 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