{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,9]],"date-time":"2026-01-09T12:41:31Z","timestamp":1767962491201,"version":"3.49.0"},"reference-count":63,"publisher":"American Society for Microbiology","issue":"6","license":[{"start":{"date-parts":[[2010,6,1]],"date-time":"2010-06-01T00:00:00Z","timestamp":1275350400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.asm.org\/non-commercial-tdm-license"}],"content-domain":{"domain":["journals.asm.org"],"crossmark-restriction":true},"short-container-title":["Eukaryot Cell"],"published-print":{"date-parts":[[2010,6]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n          <jats:p>\n            We studied staurosporine-induced cell death in the filamentous fungus\n            <jats:named-content content-type=\"genus-species\">Neurospora crassa<\/jats:named-content>\n            . The generation of reactive oxygen species during the process appears to be an important signaling event, since addition of the antioxidant glutathione prevents the effects of staurosporine on fungal growth. Selected mutants with mutations in respiratory chain complex I are extremely sensitive to the drug, stressing the involvement of complex I in programmed cell death. Following this finding, we determined that the complex I-specific inhibitor rotenone used in combination with staurosporine results in a synergistic and specific antifungal activity, likely through a concerted action on intracellular glutathione depletion. Paradoxically, the synergistic antifungal activity of rotenone and staurosporine is observed in\n            <jats:named-content content-type=\"genus-species\">N. crassa<\/jats:named-content>\n            complex I mutants and in\n            <jats:named-content content-type=\"genus-species\">Saccharomyces cerevisiae<\/jats:named-content>\n            , which lacks complex I. In addition, it is not observed when other complex I inhibitors are used instead of rotenone. These results indicate that the rotenone effect is independent of complex I inhibition. The combination of rotenone and staurosporine is effective against\n            <jats:named-content content-type=\"genus-species\">N. crassa<\/jats:named-content>\n            as well as against the common pathogens\n            <jats:named-content content-type=\"genus-species\">Aspergillus fumigatus<\/jats:named-content>\n            and\n            <jats:named-content content-type=\"genus-species\">Candida albicans<\/jats:named-content>\n            , pointing to its usefulness as an antifungal agent.\n          <\/jats:p>","DOI":"10.1128\/ec.00003-10","type":"journal-article","created":{"date-parts":[[2010,5,1]],"date-time":"2010-05-01T00:59:09Z","timestamp":1272675549000},"page":"906-914","update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":26,"title":["Rotenone Enhances the Antifungal Properties of Staurosporine"],"prefix":"10.1128","volume":"9","author":[{"given":"Ana","family":"Castro","sequence":"first","affiliation":[{"name":"IBMC, Instituto de Biologia Molecular e Celular, Universidade do Porto, Rua do Campo Alegre 823, 4150-180 Porto, Portugal;"},{"name":"UFP, Faculdade de Ci\u00eancias da Sa\u00fade, Universidade Fernando Pessoa, Rua Carlos da Maia 296, 4200-150 Porto, Portugal;"}]},{"given":"Catarina","family":"Lemos","sequence":"additional","affiliation":[{"name":"IBMC, Instituto de Biologia Molecular e Celular, Universidade do Porto, Rua do Campo Alegre 823, 4150-180 Porto, Portugal;"},{"name":"UFP, Faculdade de Ci\u00eancias da Sa\u00fade, Universidade Fernando Pessoa, Rua Carlos da Maia 296, 4200-150 Porto, Portugal;"}]},{"given":"Artur","family":"Falc\u00e3o","sequence":"additional","affiliation":[{"name":"IBMC, Instituto de Biologia Molecular e Celular, Universidade do Porto, Rua do Campo Alegre 823, 4150-180 Porto, Portugal;"}]},{"given":"Andreia S.","family":"Fernandes","sequence":"additional","affiliation":[{"name":"IBMC, Instituto de Biologia Molecular e Celular, Universidade do Porto, Rua do Campo Alegre 823, 4150-180 Porto, Portugal;"}]},{"given":"N. Louise","family":"Glass","sequence":"additional","affiliation":[{"name":"Department of Plant and Microbial Biology, University of California, Berkeley, California 94720-3102; and"}]},{"given":"Arnaldo","family":"Videira","sequence":"additional","affiliation":[{"name":"IBMC, Instituto de Biologia Molecular e Celular, Universidade do Porto, Rua do Campo Alegre 823, 4150-180 Porto, Portugal;"},{"name":"ICBAS, Instituto de Ci\u00eancias Biom\u00e9dicas de Abel Salazar, Universidade do Porto, Largo Prof. Abel Salazar 2, 4099-003 Porto, Portugal"}]}],"member":"235","reference":[{"key":"e_1_3_2_2_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0076-6879(81)77050-2"},{"key":"e_1_3_2_3_2","doi-asserted-by":"publisher","DOI":"10.2174\/138920008786049285"},{"key":"e_1_3_2_4_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbamcr.2008.01.005"},{"key":"e_1_3_2_5_2","doi-asserted-by":"publisher","DOI":"10.1038\/sj.bjp.0706556"},{"key":"e_1_3_2_6_2","doi-asserted-by":"publisher","DOI":"10.1038\/sj.onc.1204436"},{"key":"e_1_3_2_7_2","doi-asserted-by":"publisher","DOI":"10.1128\/CMR.00051-08"},{"key":"e_1_3_2_8_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jmb.2007.02.080"},{"key":"e_1_3_2_9_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M802112200"},{"key":"e_1_3_2_10_2","doi-asserted-by":"publisher","DOI":"10.1128\/MCB.23.1.163-177.2003"},{"key":"e_1_3_2_11_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbamcr.2008.04.012"},{"key":"e_1_3_2_12_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0807581105"},{"key":"e_1_3_2_13_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.bcp.2008.09.011"},{"key":"e_1_3_2_14_2","doi-asserted-by":"publisher","DOI":"10.1016\/0076-6879(71)17168-6"},{"key":"e_1_3_2_15_2","doi-asserted-by":"publisher","DOI":"10.1038\/nrg797"},{"key":"e_1_3_2_16_2","doi-asserted-by":"publisher","DOI":"10.1038\/sj.cdd.4400641"},{"key":"e_1_3_2_17_2","first-page":"55","volume-title":"Complex I and alternative dehydrogenases","author":"Duarte M.","year":"2007","unstructured":"Duarte M. 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