{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2023,7,10]],"date-time":"2023-07-10T18:15:36Z","timestamp":1689012936839},"reference-count":59,"publisher":"SAGE Publications","license":[{"start":{"date-parts":[[2009,1,1]],"date-time":"2009-01-01T00:00:00Z","timestamp":1230768000000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/journals.sagepub.com\/page\/policies\/text-and-data-mining-license"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["J\ufffdCell Death"],"published-print":{"date-parts":[[2009,1]]},"abstract":"<jats:p>Bacillus anthracis' primary virulence factor is a tripartite anthrax toxin consisting of edema factor (EF), lethal factor (LF) and protective antigen (PA). In complex with PA, EF and LF are internalized via receptor-mediated endocytosis. EF is a calmodulin-dependent adenylate cyclase that induces tissue edema. LF is a zinc-metalloprotease that cleaves members of mitogen-activated protein kinase kinases. Lethal toxin (LT: PA plus LF)-induced death of macrophages is primarily attributed to expression of the sensitive Nalp1b allele, inflammasome formation and activation of caspase-1, but early events that initiate these processes are unknown. Here we provide evidence that an early essential event in pyroptosis of alveolar macrophages is LF-mediated depletion of cellular ATP. The underlying mechanism involves interaction of LF with F<jats:sub>1<\/jats:sub>F<jats:sub>0<\/jats:sub>-complex gamma and beta subunits leading to increased ATPase activity in mitochondria. In support, mitochondrial DNA-depleted MH-S cells have decreased F<jats:sub>1<\/jats:sub>F<jats:sub>0<\/jats:sub>ATPase activity due to the lack of F<jats:sub>0<\/jats:sub>6 and F<jats:sub>0<\/jats:sub>8 polypeptides and show increased resistance to LT. We conclude that ATP depletion is an important early event in LT-induced sudden cell death and its prevention increases survival of toxin-sensitive cells.<\/jats:p>","DOI":"10.4137\/jcd.s2811","type":"journal-article","created":{"date-parts":[[2017,11,2]],"date-time":"2017-11-02T15:38:07Z","timestamp":1509637087000},"page":"JCD.S2811","source":"Crossref","is-referenced-by-count":3,"title":["ATP Depletion via Mitochondrial F<sub>1<\/sub>F<sub>0<\/sub>Complex by Lethal Factor is an Early Event in<i>B. Anthracis<\/i>-Induced Sudden Cell Death"],"prefix":"10.4137","volume":"2","author":[{"given":"Mitchell W.","family":"Woodberry","sequence":"first","affiliation":[{"name":"Medical Service Corps, Diagnostic System Division, United States Army Medical Research Institute of Infectious Diseases, Fort Detrick, Maryland 21702."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Leopoldo","family":"Aguilera-Aguirre","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology, Galveston, Texas, 77555."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Attila","family":"Bacsi","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology, Galveston, Texas, 77555."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ashok K.","family":"Chopra","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology, Galveston, Texas, 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