{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,6]],"date-time":"2026-09-06T08:50:31Z","timestamp":1788684631530,"version":"build-2803163510"},"reference-count":46,"publisher":"American Society for Microbiology","issue":"1","license":[{"start":{"date-parts":[[2013,1,1]],"date-time":"2013-01-01T00:00:00Z","timestamp":1356998400000},"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":["Antimicrob Agents Chemother"],"published-print":{"date-parts":[[2013,1]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    Mitochondrial dysfunction in pathogenic fungi or model yeast causes altered susceptibilities to antifungal drugs. Here we have characterized the role of mitochondrial complex I (CI) of\n                    <jats:named-content xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" content-type=\"genus-species\" xlink:type=\"simple\">Candida albicans<\/jats:named-content>\n                    in antifungal susceptibility. Inhibitors of CI to CV, except for CII, increased the susceptibility of both patient and lab isolates, even those with a resistance phenotype. In addition, in a\n                    <jats:named-content xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" content-type=\"genus-species\" xlink:type=\"simple\">C. albicans<\/jats:named-content>\n                    library of 12 CI null mutants, 10 displayed hypersusceptibility to fluconazole and were severely growth inhibited on glycerol, implying a role for each gene in cell respiration. We chose two other hypersusceptible null mutants of\n                    <jats:named-content xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" content-type=\"genus-species\" xlink:type=\"simple\">C. albicans<\/jats:named-content>\n                    , the\n                    <jats:italic>goa1<\/jats:italic>\n                    \u0394 and\n                    <jats:italic>ndh51<\/jats:italic>\n                    \u0394 mutants, for transcriptional profiling by RNA-Seq. Goa1p is required for CI activity, while Ndh51p is a CI subunit. RNA-Seq revealed that both the\n                    <jats:italic>ndh51<\/jats:italic>\n                    \u0394 mutant and especially the\n                    <jats:italic>goa1<\/jats:italic>\n                    \u0394 mutant had significant downregulation of transporter genes, including\n                    <jats:italic>CDR1<\/jats:italic>\n                    and\n                    <jats:italic>CDR2<\/jats:italic>\n                    , which encode efflux proteins. In the\n                    <jats:italic>goa1<\/jats:italic>\n                    \u0394 mutant, we noted the downregulation of genes required for the biogenesis and replication of peroxisomes, as well as metabolic pathways assigned to peroxisomes such as \u03b2-oxidation of fatty acids, glyoxylate bypass, and acetyl coenzyme A (acetyl-CoA) transferases that are known to shuttle acetyl-CoA between peroxisomes and mitochondria. The transcriptome profile of the\n                    <jats:italic>ndh51<\/jats:italic>\n                    \u0394 mutant did not include downregulation of peroxisome genes but had, instead, extensive downregulation of the ergosterol synthesis gene family. Our data establish that cell energy is required for azole susceptibility and that downregulation of efflux genes may be an outcome of that dysfunction. However, there are mutant-specific changes that may also increase the susceptibility of both of these\n                    <jats:named-content xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" content-type=\"genus-species\" xlink:type=\"simple\">C. albicans<\/jats:named-content>\n                    mutants to azoles.\n                  <\/jats:p>","DOI":"10.1128\/aac.01520-12","type":"journal-article","created":{"date-parts":[[2012,11,13]],"date-time":"2012-11-13T07:24:10Z","timestamp":1352791450000},"page":"532-542","update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":90,"title":["Azole Susceptibility and Transcriptome Profiling in Candida albicans Mitochondrial Electron Transport Chain Complex I Mutants"],"prefix":"10.1128","volume":"57","author":[{"given":"Nuo","family":"Sun","sequence":"first","affiliation":[{"name":"Georgetown University Medical Center, Department of Microbiology and Immunology, Washington, DC, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"William","family":"Fonzi","sequence":"additional","affiliation":[{"name":"Georgetown University Medical Center, Department of Microbiology and Immunology, Washington, DC, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hui","family":"Chen","sequence":"additional","affiliation":[{"name":"Georgetown University Medical Center, Department of Microbiology and Immunology, Washington, DC, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaodong","family":"She","sequence":"additional","affiliation":[{"name":"Georgetown University Medical Center, Department of Microbiology and Immunology, Washington, DC, USA"},{"name":"Institute of Dermatology, Chinese Academy of Medical Sciences (CAMS) and Peking Union Medical College (PUMC), Nanjing, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lulu","family":"Zhang","sequence":"additional","affiliation":[{"name":"Georgetown University Medical Center, Department of Microbiology and Immunology, Washington, DC, USA"},{"name":"Department of Dermatology, Jiangsu Province Hospital of Traditional Chinese Medicine, Nanjing, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lixin","family":"Zhang","sequence":"additional","affiliation":[{"name":"CAS Key Laboratory of Pathogenic Microbiology and Immunology, Chinese Academy of Science, Institute of Microbiology, Beijing, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Richard","family":"Calderone","sequence":"additional","affiliation":[{"name":"Georgetown University Medical Center, Department of Microbiology and Immunology, Washington, DC, 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