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Here we show that human lung adenocarcinoma tissue expresses high levels of hydrogen sulfide (H<jats:sub>2<\/jats:sub>S) producing enzymes, namely, cystathionine beta-synthase (CBS), cystathionine gamma lyase (CSE) and 3-mercaptopyruvate sulfurtransferase (3-MST), in comparison to adjacent lung tissue. In cultured lung adenocarcinoma but not in normal lung epithelial cells elevated H<jats:sub>2<\/jats:sub>S stimulates mitochondrial DNA repair through sulfhydration of EXOG, which, in turn, promotes mitochondrial DNA repair complex assembly, thereby enhancing mitochondrial DNA repair capacity. In addition, inhibition of H<jats:sub>2<\/jats:sub>S-producing enzymes suppresses critical bioenergetics parameters in lung adenocarcinoma cells. Together, inhibition of H<jats:sub>2<\/jats:sub>S-producing enzymes sensitize lung adenocarcinoma cells to chemotherapeutic agents via induction of mitochondrial dysfunction as shown in <jats:italic>in vitro<\/jats:italic> and <jats:italic>in vivo<\/jats:italic> models, suggesting a novel mechanism to overcome tumor chemoresistance.<\/jats:p>","DOI":"10.1038\/srep36125","type":"journal-article","created":{"date-parts":[[2016,11,3]],"date-time":"2016-11-03T10:20:39Z","timestamp":1478168439000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":102,"title":["Inhibition of hydrogen sulfide biosynthesis sensitizes lung adenocarcinoma to chemotherapeutic drugs by inhibiting mitochondrial DNA repair and suppressing cellular bioenergetics"],"prefix":"10.1038","volume":"6","author":[{"given":"Bartosz","family":"Szczesny","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michela","family":"Marcatti","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John R.","family":"Zatarain","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nadiya","family":"Druzhyna","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John E.","family":"Wiktorowicz","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"P\u00e9ter","family":"Nagy","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mark R.","family":"Hellmich","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Csaba","family":"Szabo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2016,11,3]]},"reference":[{"key":"BFsrep36125_CR1","doi-asserted-by":"crossref","first-page":"917","DOI":"10.1038\/nrd2425","volume":"6","author":"C Szabo","year":"2007","unstructured":"Szabo, C. 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