{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,18]],"date-time":"2026-09-18T05:04:31Z","timestamp":1789707871490,"version":"4.0.1"},"reference-count":43,"publisher":"Wiley","license":[{"start":{"date-parts":[[2026,9,17]],"date-time":"2026-09-17T00:00:00Z","timestamp":1789603200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2026,9,17]],"date-time":"2026-09-17T00:00:00Z","timestamp":1789603200000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100001407","name":"Department of Biotechnology, Ministry of Science and Technology, India","doi-asserted-by":"publisher","award":["BT\/PR\/Centre\/03\/2011\u2010Phase\u2010II"],"award-info":[{"award-number":["BT\/PR\/Centre\/03\/2011\u2010Phase\u2010II"]}],"id":[{"id":"10.13039\/501100001407","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Molecular Microbiology"],"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    Carbon catabolite repression (CCR) enables fungi to preferentially utilize favorable carbon sources through global transcriptional control. In filamentous fungi, CCR is classically attributed to the C2H2 zinc\u2010finger repressor Mig1\/CreA; however, residual repression following Mig1 disruption suggests additional regulatory layers in\n                    <jats:italic>Talaromyces pinophilus<\/jats:italic>\n                    (previously called\n                    <jats:italic>Penicillium funiculosum<\/jats:italic>\n                    NCIM1228). Here, we identify Mig3, a previously uncharacterized, Eurotiales\u2010specific C2H2 transcription factor that functions redundantly with Mig1 in CCR. Mig3 contains conserved N\u2010terminal zinc\u2010finger motifs and a fungal transcription factor middle homology region and binds canonical Mig1 response elements with higher DNA affinity. Genetic analyses reveal that simultaneous loss of Mig1 and Mig3 is synthetically lethal, indicating an essential shared function beyond carbon repression. Integrative transcriptomic, chromatin immunoprecipitation sequencing, and proteomic analyses demonstrate that Mig1 and Mig3 directly regulate genes encoding mitochondrial and ribosomal components, including key factors involved in oxidative phosphorylation, while repressing genes required for alternative carbon metabolism. Loss of either repressor compromises expression of respiratory and ribosomal genes and confers hypersensitivity to mitochondrial and ribosomal inhibitors. In addition, both repressors physically associate with mitochondrial, ribosomal, and central metabolic proteins, suggesting coordination of transcriptional and posttranscriptional regulatory mechanisms. Together, our findings redefine fungal catabolite repressors as metabolic gatekeepers that couple CCR to mitochondrial and ribosome biogenesis, thereby controlling the metabolic switch between core cellular growth processes and enzyme secretion.\n                  <\/jats:p>","DOI":"10.1111\/mmi.70116","type":"journal-article","created":{"date-parts":[[2026,9,18]],"date-time":"2026-09-18T04:25:04Z","timestamp":1789705504000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Synthetic Lethality of Fungal Catabolite Repressors Reveals Essential Coupling of Carbon Repression With Mitochondrial and Ribosomal Gene Expression"],"prefix":"10.1111","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8628-044X","authenticated-orcid":false,"given":"Anmoldeep","family":"Randhawa","sequence":"first","affiliation":[{"name":"Microbial Engineering Group International Centre for Genetic Engineering and Biotechnology  New Delhi India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0005-7853-7638","authenticated-orcid":false,"given":"Raubins","family":"Kumar","sequence":"additional","affiliation":[{"name":"Microbial Engineering Group International Centre for Genetic Engineering and Biotechnology  New Delhi India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0008-8980-166X","authenticated-orcid":false,"given":"Sonal","family":"Kapoor","sequence":"additional","affiliation":[{"name":"Microbial Engineering Group International Centre for Genetic Engineering and Biotechnology  New Delhi India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4151-3393","authenticated-orcid":false,"given":"Mayank","family":"Gupta","sequence":"additional","affiliation":[{"name":"Microbial Engineering Group International Centre for Genetic Engineering and Biotechnology  New Delhi India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6558-4612","authenticated-orcid":false,"given":"Syed Shams","family":"Yazdani","sequence":"additional","affiliation":[{"name":"Microbial Engineering Group International Centre for Genetic Engineering and Biotechnology  New Delhi India"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,9,17]]},"reference":[{"key":"e_1_2_13_2_1","doi-asserted-by":"crossref","DOI":"10.3390\/ijms19010048","article-title":"Carbon Catabolite Repression in Filamentous Fungi","volume":"19","author":"Adnan M.","year":"2018","journal-title":"International Journal of Molecular Sciences"},{"key":"e_1_2_13_3_1","doi-asserted-by":"crossref","first-page":"93","DOI":"10.1016\/j.fgb.2014.10.009","article-title":"Defining the Genome\u2010Wide Role of CRE1 During Carbon Catabolite Repression in Trichoderma reesei Using RNA\u2010Seq Analysis","volume":"73","author":"Antoni\u00eato A. C. C.","year":"2014","journal-title":"Fungal Genetics and Biology"},{"key":"e_1_2_13_4_1","doi-asserted-by":"crossref","DOI":"10.1128\/mbio.03734-21","article-title":"Carbon Catabolite Repression Governs Diverse Physiological Processes and Development in Aspergillus nidulans","volume":"13","author":"Chen Y.","year":"2022","journal-title":"mBio"},{"key":"e_1_2_13_5_1","doi-asserted-by":"crossref","DOI":"10.1128\/mBio.03146-20","article-title":"Carbon Catabolite Repression in Filamentous Fungi Is Regulated by Phosphorylation of the Transcription Factor CreA","volume":"12","author":"De Assis L. J.","year":"2021","journal-title":"mBio"},{"key":"e_1_2_13_6_1","doi-asserted-by":"crossref","first-page":"253","DOI":"10.1006\/fgbi.1999.1121","article-title":"Carbon Regulation of Ribosomal Genes in Neurospora crassa Occurs by a Mechanism Which Does Not Require Cre\u20101, the Homologue of the Aspergillus Carbon Catabolite Repressor, CreA","volume":"26","author":"De La Serna I.","year":"1999","journal-title":"Fungal Genetics and Biology"},{"key":"e_1_2_13_7_1","doi-asserted-by":"crossref","first-page":"1069","DOI":"10.1093\/genetics\/142.4.1069","article-title":"Functional Analysis of the PUT3 Transcriptional Activator of the Proline Utilization Pathway in \n                     Saccharomyces cerevisiae","volume":"142","author":"Etages S. A. G. D.","year":"1996","journal-title":"Genetics"},{"key":"e_1_2_13_8_1","doi-asserted-by":"crossref","first-page":"1061","DOI":"10.1128\/EC.2.5.1061-1068.2003","article-title":"Sfp1 Plays a Key Role in Yeast Ribosome Biogenesis","volume":"2","author":"Fingerman I.","year":"2003","journal-title":"Eukaryotic Cell"},{"key":"e_1_2_13_9_1","doi-asserted-by":"crossref","first-page":"244","DOI":"10.1186\/s13068-021-02092-9","article-title":"Carbon Catabolite Repression Involves Physical Interaction of the Transcription Factor CRE1\/CreA and the Tup1\u2013Cyc8 Complex in Penicillium oxalicum and Trichoderma reesei","volume":"14","author":"Hu Y.","year":"2021","journal-title":"Biotechnology for Biofuels"},{"key":"e_1_2_13_10_1","doi-asserted-by":"crossref","first-page":"5629","DOI":"10.1093\/nar\/gkw168","article-title":"The Hsp70 Homolog Ssb and the 14\u20103\u20103 Protein Bmh1 Jointly Regulate Transcription of Glucose Repressed Genes in \n                     Saccharomyces cerevisiae","volume":"44","author":"H\u00fcbscher V.","year":"2016","journal-title":"Nucleic Acids Research"},{"key":"e_1_2_13_11_1","doi-asserted-by":"crossref","DOI":"10.1016\/j.jbc.2022.102494","article-title":"Elucidation of the Interaction Proteome of Mitochondrial Chaperone Hsp78 Highlights Its Role in Protein Aggregation During Heat Stress","volume":"298","author":"Jaworek W.","year":"2022","journal-title":"Journal of Biological Chemistry"},{"key":"e_1_2_13_12_1","doi-asserted-by":"crossref","DOI":"10.1371\/journal.pgen.1008582","article-title":"Roles of \n                     Candida albicans\n                   Mig1 and Mig2 in Glucose Repression, Pathogenicity Traits, and SNF1 Essentiality","volume":"16","author":"Lagree K.","year":"2020","journal-title":"PLoS Genetics"},{"key":"e_1_2_13_13_1","doi-asserted-by":"crossref","DOI":"10.1371\/journal.pbio.1001325","article-title":"Bet Hedging in Yeast by Heterogeneous, Age\u2010Correlated Expression of a Stress Protectant","volume":"10","author":"Levy S. F.","year":"2012","journal-title":"PLoS Biology"},{"key":"e_1_2_13_14_1","doi-asserted-by":"crossref","DOI":"10.1186\/s13068-017-0915-9","article-title":"Cellulase Hyper\u2010Production by Trichoderma reesei Mutant SEU\u20107 on Lactose","volume":"10","author":"Li C.","year":"2017","journal-title":"Biotechnology for Biofuels"},{"key":"e_1_2_13_15_1","doi-asserted-by":"crossref","first-page":"1494","DOI":"10.1016\/j.procbio.2010.05.031","article-title":"Roles of Extracellular Lactose Hydrolysis in Cellulase Production by Trichoderma reesei Rut C30 Using Lactose as Inducing Substrate","volume":"45","author":"Lo C.\u2010M.","year":"2010","journal-title":"Process Biochemistry"},{"key":"e_1_2_13_16_1","doi-asserted-by":"crossref","first-page":"1377","DOI":"10.1093\/genetics\/150.4.1377","article-title":"Characterization of Three Related Glucose Repressors and Genes They Regulate in \n                     Saccharomyces cerevisiae","volume":"150","author":"Lutfiyya L. L.","year":"1998","journal-title":"Genetics"},{"key":"e_1_2_13_17_1","first-page":"85","volume-title":"Environmental and Microbial Relationships","author":"Magan N.","year":"2007"},{"key":"e_1_2_13_18_1","doi-asserted-by":"crossref","first-page":"6491","DOI":"10.1128\/MCB.17.11.6491","article-title":"Xbp1, a Stress\u2010Induced Transcriptional Repressor of the \n                     Saccharomyces cerevisiae\n                   Swi4\/Mbp1 Family","volume":"17","author":"Mai B.","year":"1997","journal-title":"Molecular and Cellular Biology"},{"key":"e_1_2_13_19_1","doi-asserted-by":"crossref","first-page":"269","DOI":"10.1128\/jb.73.2.269-278.1957","article-title":"Induction of Cellulase in Trichoderma Viride as Influenced by Carbon Sources and Metals","volume":"73","author":"Mandels M.","year":"1957","journal-title":"Journal of Bacteriology"},{"key":"e_1_2_13_20_1","doi-asserted-by":"crossref","DOI":"10.1371\/journal.pbio.1001764","article-title":"Different Levels of Catabolite Repression Optimize Growth in Stable and Variable Environments","volume":"12","author":"New A. M.","year":"2014","journal-title":"PLoS Biology"},{"key":"e_1_2_13_21_1","doi-asserted-by":"crossref","first-page":"71","DOI":"10.1186\/s13068-017-0752-x","article-title":"Comparative Insights Into the Saccharification Potentials of a Relatively Unexplored but Robust Penicillium funiculosum Glycoside Hydrolase 7 Cellobiohydrolase","volume":"10","author":"Ogunmolu F. E.","year":"2017","journal-title":"Biotechnology for Biofuels"},{"key":"e_1_2_13_22_1","doi-asserted-by":"crossref","first-page":"4342","DOI":"10.1021\/acs.jproteome.5b00542","article-title":"Proteomics Insights Into the Biomass Hydrolysis Potentials of a Hypercellulolytic Fungus Penicillium funiculosum","volume":"14","author":"Ogunmolu F. E.","year":"2015","journal-title":"Journal of Proteome Research"},{"key":"e_1_2_13_23_1","doi-asserted-by":"crossref","first-page":"49","DOI":"10.1016\/j.procbio.2020.02.029","article-title":"Engineered Penicillium funiculosum Produces Potent Lignocellulolytic Enzymes for Saccharification of Various Pretreated Biomasses","volume":"92","author":"Ogunyewo O. A.","year":"2020","journal-title":"Process Biochemistry"},{"key":"e_1_2_13_24_1","doi-asserted-by":"crossref","DOI":"10.1186\/s13068-023-02399-9","article-title":"Systematic Identification of CAZymes and Transcription Factors in the Hypercellulolytic Fungus Penicillium funiculosum NCIM1228 Involved in Lignocellulosic Biomass Degradation","volume":"16","author":"Pasari N.","year":"2023","journal-title":"Biotechnology for Biofuels"},{"key":"e_1_2_13_25_1","doi-asserted-by":"crossref","DOI":"10.1016\/j.tcsw.2021.100050","article-title":"CreA\u2010Mediated Repression of Gene Expression Occurs at Low Monosaccharide Levels During Fungal Plant Biomass Conversion in a Time and Substrate Dependent Manner","volume":"7","author":"Peng M.","year":"2021","journal-title":"Cell Surface"},{"key":"e_1_2_13_26_1","doi-asserted-by":"crossref","DOI":"10.1186\/s13068-023-02448-3","article-title":"Calcium Signaling Positively Regulates Cellulase Translation and Secretion in a Clr\u20102\u2010Overexpressing, Catabolically Derepressed Strain of Penicillium funiculosum","volume":"17","author":"Randhawa A.","year":"2024","journal-title":"Biotechnology for Biofuels"},{"key":"e_1_2_13_27_1","doi-asserted-by":"crossref","first-page":"15","DOI":"10.1186\/s13068-018-1011-5","article-title":"Disruption of Zinc Finger DNA Binding Domain in Catabolite Repressor Mig1 Increases Growth Rate, Hyphal Branching, and Cellulase Expression in Hypercellulolytic Fungus Penicillium funiculosum NCIM1228","volume":"11","author":"Randhawa A.","year":"2018","journal-title":"Biotechnology for Biofuels"},{"key":"e_1_2_13_28_1","doi-asserted-by":"crossref","DOI":"10.1002\/jobm.202400658","article-title":"AMPK Activates Cellulase Secretion in Penicillium funiculosum by Downregulating P\u2010HOG1 MAPK Levels","volume":"65","author":"Randhawa A.","year":"2024","journal-title":"Journal of Basic Microbiology"},{"key":"e_1_2_13_29_1","doi-asserted-by":"crossref","first-page":"335","DOI":"10.1534\/genetics.116.187872","article-title":"Diverse Regulation of the CreA Carbon Catabolite Repressor in Aspergillus nidulans","volume":"203","author":"Ries L. N. A.","year":"2016","journal-title":"Genetics"},{"key":"e_1_2_13_30_1","doi-asserted-by":"crossref","DOI":"10.1371\/journal.pgen.1003871","article-title":"Yeast Tdh3 (Glyceraldehyde 3\u2010Phosphate Dehydrogenase) Is a Sir2\u2010Interacting Factor That Regulates Transcriptional Silencing and rDNA Recombination","volume":"9","author":"Ringel A. E.","year":"2013","journal-title":"PLoS Genetics"},{"key":"e_1_2_13_31_1","doi-asserted-by":"crossref","first-page":"10135","DOI":"10.1074\/jbc.M413731200","article-title":"Activation of the Iron Regulon by the Yeast Aft1\/Aft2 Transcription Factors Depends on Mitochondrial but Not Cytosolic Iron\u2010Sulfur Protein Biogenesis","volume":"280","author":"Rutherford J. C.","year":"2005","journal-title":"Journal of Biological Chemistry"},{"key":"e_1_2_13_32_1","doi-asserted-by":"crossref","DOI":"10.3390\/jof9080834","article-title":"Strategies for the Development of Industrial Fungal Producing Strains","volume":"9","author":"Salazar\u2010Cerezo S.","year":"2023","journal-title":"Journal of Fungi"},{"key":"e_1_2_13_33_1","doi-asserted-by":"crossref","first-page":"139","DOI":"10.1007\/s00294-003-0381-8","article-title":"Transcriptional Control of Nonfermentative Metabolism in the Yeast \n                     Saccharomyces cerevisiae","volume":"43","author":"Sch\u00fcller H.\u2010J.","year":"2003","journal-title":"Current Genetics"},{"key":"e_1_2_13_34_1","doi-asserted-by":"crossref","first-page":"28","DOI":"10.1006\/fgbi.1997.0989","article-title":"Null Alleles of creA, the Regulator of Carbon Catabolite Repression in Aspergillus nidulans","volume":"22","author":"Shroff R. A.","year":"1997","journal-title":"Fungal Genetics and Biology"},{"key":"e_1_2_13_35_1","doi-asserted-by":"crossref","first-page":"103","DOI":"10.1016\/0014-5793(95)01255-5","article-title":"Crel, the Carbon Catabolite Repressor Protein From Trichoderma reesei","volume":"376","author":"Strauss J.","year":"1995","journal-title":"FEBS Letters"},{"key":"e_1_2_13_36_1","doi-asserted-by":"crossref","DOI":"10.1371\/journal.pone.0025654","article-title":"Identification of the CRE\u20101 Cellulolytic Regulon in Neurospora crassa","volume":"6","author":"Sun J.","year":"2011","journal-title":"PLoS One"},{"key":"e_1_2_13_37_1","doi-asserted-by":"crossref","DOI":"10.1371\/journal.pbio.1002042","article-title":"Population Diversification in a Yeast Metabolic Program Promotes Anticipation of Environmental Shifts","volume":"13","author":"Venturelli O. S.","year":"2015","journal-title":"PLoS Biology"},{"key":"e_1_2_13_38_1","doi-asserted-by":"crossref","first-page":"101","DOI":"10.1111\/ppa.12246","article-title":"Molecular and Biochemical Characterization of Boscalid Resistance in Laboratory Mutants of Sclerotinia sclerotiorum","volume":"64","author":"Wang Y.","year":"2015","journal-title":"Plant Pathology"},{"key":"e_1_2_13_39_1","doi-asserted-by":"crossref","first-page":"72","DOI":"10.1016\/j.fgb.2015.11.003","article-title":"Tet\u2010On, or Tet\u2010Off, That Is the Question: Advanced Conditional Gene Expression in Aspergillus","volume":"89","author":"Wanka F.","year":"2016","journal-title":"Fungal Genetics and Biology"},{"key":"e_1_2_13_40_1","doi-asserted-by":"crossref","first-page":"195","DOI":"10.1016\/S0378-1119(99)00510-7","article-title":"RLR1 (THO2), Required for Expressing lacZ Fusions in Yeast, Is Conserved From Yeast to Humans and Is a Suppressor of SIN4","volume":"243","author":"West R. W.","year":"2000","journal-title":"Gene"},{"key":"e_1_2_13_41_1","doi-asserted-by":"crossref","DOI":"10.1186\/1471-2164-9-601","article-title":"Combinatorial Control of Gene Expression by the Three Yeast Repressors Mig1, Mig2 and Mig3","volume":"9","author":"Westholm J. O.","year":"2008","journal-title":"BMC Genomics"},{"key":"e_1_2_13_42_1","doi-asserted-by":"crossref","DOI":"10.1371\/journal.pgen.1004500","article-title":"VIB1, a Link Between Glucose Signaling and Carbon Catabolite Repression, Is Essential for Plant Cell Wall Degradation by Neurospora crassa","volume":"10","author":"Xiong Y.","year":"2014","journal-title":"PLoS Genetics"},{"key":"e_1_2_13_43_1","doi-asserted-by":"crossref","first-page":"107","DOI":"10.1186\/s40643-021-00461-8","article-title":"From Induction to Secretion: A Complicated Route for Cellulase Production in Trichoderma reesei","volume":"8","author":"Yan S.","year":"2021","journal-title":"Bioresources and Bioprocessing"},{"key":"e_1_2_13_44_1","doi-asserted-by":"crossref","first-page":"677","DOI":"10.1016\/j.molcel.2018.01.028","article-title":"The Yeast INO80 Complex Operates as a Tunable DNA Length\u2010Sensitive Switch to Regulate Nucleosome Sliding","volume":"69","author":"Zhou C. Y.","year":"2018","journal-title":"Molecular Cell"}],"container-title":["Molecular Microbiology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/mmi.70116","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1111\/mmi.70116","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/mmi.70116","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,9,18]],"date-time":"2026-09-18T04:25:09Z","timestamp":1789705509000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/mmi.70116"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,9,17]]},"references-count":43,"alternative-id":["10.1111\/mmi.70116"],"URL":"https:\/\/doi.org\/10.1111\/mmi.70116","archive":["Portico"],"relation":{},"ISSN":["0950-382X","1365-2958"],"issn-type":[{"value":"0950-382X","type":"print"},{"value":"1365-2958","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,9,17]]},"assertion":[{"value":"2026-02-23","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-09-08","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-09-17","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"mmi.70116"}}