Atg8 and Ire1 in combination regulate the autophagy-related endoplasmic reticulum stress response in Candida albicans |
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| Affiliation: | 1. Instituto de Química San Luis (INQUISAL), CONICET, Chacabuco 917, 5700 San Luis, Argentina;2. Facultad de Química, Bioquímica y Farmacia, Universidad Nacional de San Luis, Chacabuco 917, 5700 San Luis, Argentina;3. Division of Basic Biomedical Sciences Sanford School of Medicine, University of South Dakota, Vermillion, SD, USA;1. Institute of Biomedical Sciences, University of São Paulo, Prof. Lineu Prestes Avenue, 1374 – 05508-000, São Paulo/SP, Brazil;2. Department of Medicine, Federal University of São Paulo, Botucatu Street, 720 – 04039-032, São Paulo/SP, Brazil;1. Cellular and Molecular Genetics Laboratory, Institute of Biological Sciences, Federal University of Minas Gerais, Belo Horizonte, MG, Brazil;2. Postgraduate Program in Microbiology, Institute of Biology, Federal University of Bahia, Salvador, BA, Brazil;3. Postgraduate Program in Immunology, Institute of Health Sciences, Federal University of Bahia, Salvador, BA, Brazil;4. Department of Veterinary Science, University of Messina (Italy), Polo Universitario dell’Annunziata, 98168 Messina (ME), Italy;5. School of Biosciences and Veterinary Medicine, University of Camerino (Italy), Via Circonvallazione 93/95, 62024 Matelica (MC), Italy;6. Department of Veterinary Medicine and Epidemiology, University of California, Davis, CA, USA;7. Institute of Veterinary Medicine, University of Göttingen, Burckhardtweg 2, Göttingen, Germany;8. Department of Computer Science, Federal University of Uberlandia, Uberlandia, Brazil;9. Molecular and Computational Biology of Fungi Laboratory Department of Microbiology, Institute of Biological Sciences, Federal University of Minas Gerais Brazil;10. Department of Biotechnology, Institute of Health Sciences, Federal University of Bahia, Salvador, BA, Brazil;1. Department of Microbiology and Immunology, Uniformed Services University of the Health Sciences, Bethesda, MD, USA;2. Henry M. Jackson Foundation for the Advancement of Military Medicine, Rockville, MD, USA;3. Biomedical Instrumentation Center, Uniformed Services University of the Health Sciences, Bethesda, MD, USA |
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| Abstract: | The unfolded protein response (UPR) is an important pathway to prevent endoplasmic reticulum (ER) stress in eukaryotic cells. In Saccharomyces cerevisiae, Ire1 is a key regulatory factor required for HAC1 gene splicing for further production of functional Hac1 and activation of UPR gene expression. Autophagy is another mechanism involved in the attenuation of ER stress by ER-phagy, and Atg8 is a core protein in autophagy. Both autophagy and UPR are critical for ER stress response, but whether they act individually or in combination in Candida albicans is unknown. In this study, we explored the interaction between Ire1 and the autophagy protein Atg8 for the ER stress response by constructing the atg8Δ/Δire1Δ/Δ double mutant in the pathogenic fungus C. albicans. Compared to the single mutants atg8Δ/Δ or ire1Δ/Δ, atg8Δ/Δire1Δ/Δ exhibited much higher sensitivity to various ER stress-inducing agents and more severe attenuation of UPR gene expression under ER stress. Further investigations showed that the double mutant had a defect in ER-phagy, which was associated with attenuated vacuolar fusion under ER stress. This study revealed that Ire1 and Atg8 in combination function in the activation of the UPR and ER-phagy to maintain ER homeostasis under ER stress in C. albicans. |
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| Keywords: | Endoplasmic reticulum Ire1 Unfolded protein response ER-Phagy UPR" },{" #name" :" keyword" ," $" :{" id" :" kwrd0040" }," $$" :[{" #name" :" text" ," _" :" unfolded protein response ER" },{" #name" :" keyword" ," $" :{" id" :" kwrd0050" }," $$" :[{" #name" :" text" ," _" :" endoplasmic reticulum TM" },{" #name" :" keyword" ," $" :{" id" :" kwrd0060" }," $$" :[{" #name" :" text" ," _" :" tunicamycin autophagy-related genes TEM" },{" #name" :" keyword" ," $" :{" id" :" kwrd0080" }," $$" :[{" #name" :" text" ," _" :" transmission electron microscopy YNB" },{" #name" :" keyword" ," $" :{" id" :" kwrd0090" }," $$" :[{" #name" :" text" ," _" :" yeast nitrogen base FLU" },{" #name" :" keyword" ," $" :{" id" :" kwrd0100" }," $$" :[{" #name" :" text" ," _" :" fluorescence intensity DTT" },{" #name" :" keyword" ," $" :{" id" :" kwrd0110" }," $$" :[{" #name" :" text" ," _" :" dithiothreitol β-ME" },{" #name" :" keyword" ," $" :{" id" :" kwrd0120" }," $$" :[{" #name" :" text" ," _" :" β-mercaptoethanol EGTA" },{" #name" :" keyword" ," $" :{" id" :" kwrd0130" }," $$" :[{" #name" :" text" ," _" :" glycol-bis-(2-aminoethylether)-N,N,N′,N′-tetraacetic acid |
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