Global gene expression analysis of Aspergillus nidulans reveals metabolic shift and transcription suppression under hypoxia
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Hypoxia imposes a challenge upon most filamentous fungi that require oxygen for proliferation. Here, we used whole genome DNA microarrays to investigate global transcriptional changes in Aspergillus nidulans gene expression after exposure to hypoxia followed by normoxia. Aeration affected the expression of 2,864 genes (27% of the total number of genes in the fungus), of which 50% were either induced or repressed under hypoxic conditions. Up-regulated genes included those for glycolysis, ethanol production, the tricarboxylic acid (TCA) cycle, and for the γ-aminobutyrate (GABA) shunt that bypasses two steps of the TCA cycle. Ethanol and lactate production under hypoxic conditions indicated that glucose was fermented to these compounds via the glycolytic pathway. Since the GABA shunt bypasses the NADH-generating reaction of the TCA cycle catalyzed by oxoglutarate dehydrogenase, hypoxic A. nidulans cells eliminated excess NADH. Hypoxia down-regulated some genes involved in transcription initiation by RNA polymerase II, and lowered the cellular mRNA content. These functions were resumed by re-oxygenation, indicating that A. nidulans controls global transcription to adapt to a hypoxic environment. This study is the first to show that hypoxia elicits systematic transcriptional responses in A. nidulans.
KeywordsFungus Fermentation Environmental stress Glutamate dehydrogenase Respiration
We thank Norma Foster for critical reading of the manuscript. This study was partly supported by the Bio-oriented Technology Research Advancement Institution, and a Grant-in-Aid for Scientific Research from Ministry of Education, Science, Culture and Sports of Japan.
- Bonaccorsi ED, Ferreira AJ, Chambergo FS, Ramos AS, Mantovani MC, Farah JP, Sorio CS, Gombert AK, Tonso A, El-Dorry H (2006) Transcriptional response of the obligatory aerobe Trichoderma reesei to hypoxia and transient anoxia: implications for energy production and survival in the absence of oxygen. Biochemistry 45:3912–3924CrossRefPubMedGoogle Scholar
- Daran-Lapujade P, Rossell S, van Gulik WM, Luttik MA, de Groot MJ, Slijper M, Heck AJ, Daran JM, de Winde JH, Westerhoff HV, Pronk JT, Bakker BM (2007) The fluxes through glycolytic enzymes in Saccharomyces cerevisiae are predominantly regulated at posttranscriptional levels. Proc Natl Acad Sci USA 104:15753–15758CrossRefPubMedGoogle Scholar
- Di Pierro D, Tavazzi B, Perno CF, Bartolini M, Balestra E, Caliò R, Giardina B, Lazzarino G (1997) An ion-pairing high-performance liquid chromatographic method for the direct simultaneous determination of nucleotides, deoxynucleotides, nicotinic coenzymes, oxypurines, nucleosides, and bases in perchloric acid cell extracts. Anal Biochem 231:407–412CrossRefGoogle Scholar
- Giaever G, Chu AM, Ni L, Connelly C, Riles L, Véronneau S, Dow S, Lucau-Danila A, Anderson K, André B, Arkin AP, Astromoff A, El-Bakkoury M, Bangham R, Benito R, Brachat S, Campanaro S, Curtiss M, Davis K, Deutschbauer A, Entian KD, Flaherty P, Foury F, Garfinkel DJ, Gerstein M, Gotte D, Güldener U, Hegemann JH, Hempel S, Herman Z, Jaramillo DF, Kelly DE, Kelly SL, Kötter P, LaBonte D, Lamb DC, Lan N, Liang H, Liao H, Liu L, Luo C, Lussier M, Mao R, Menard P, Ooi SL, Revuelta JL, Roberts CJ, Rose M, Ross-Macdonald P, Scherens B, Schimmack G, Shafer B, Shoemaker DD, Sookhai-Mahadeo S, Storms RK, Strathern JN, Valle G, Voet M, Volckaert G, Wang CY, Ward TR, Wilhelmy J, Winzeler EA, Yang Y, Yen G, Youngman E, Yu K, Bussey H, Boeke JD, Snyder M, Philippsen P, Davis RW, Johnston M (2002) Functional profiling of the Saccharomyces cerevisiae genome. Nature 418:387–391CrossRefPubMedGoogle Scholar
- Shimizu S, Eguchi Y, Kamiike W, Waguri S, Uchiyama Y, Matsuda H, Tsujimoto Y (1996) Retardation of chemical hypoxia-induced necrotic cell death by Bcl-2 and ICE inhibitors: possible involvement of common mediators in apoptotic and necrotic signal transductions. Oncogene 12:2045–2050PubMedGoogle Scholar
- van der Werf MJ, Pieterse B, van Luijk N, Schuren F, der Vat B, Overkamp K, Jellema RH (2006) Multivariate analysis of microarray data by principal component discriminant analysis: prioritizing relevant transcripts linked to the degradation of different carbohydrates in Pseudomonas putida S12. Microbiology 152:257–272CrossRefPubMedGoogle Scholar
- Zhou Z, Takaya N, Sakairi MA, Shoun H (2001) Oxygen requirement for denitrification by the fungus Fusarium oxysporum. Arch Microbiol 175:19–25Google Scholar
- Zhou Z, Takaya N, Nakamura A, Yamaguchi M, Takeo K, Shoun H (2002) Ammonia fermentation, a novel anoxic metabolism of nitrate by fungi. J Biol Chem 277:1892–1896Google Scholar