TY - JOUR AU - Bjedov, I. AU - Cochemé, H.M. AU - Foley, A. AU - Wieser, D. AU - Woodling, N.S. AU - Castillo-Quan, J.I. AU - Norvaisas, P. AU - Lujan, C. AU - Regan, J. AU - Toivonen, J.M. AU - Murphy, M.P. AU - Thornton, J. AU - Kinghorn, K.J. AU - Neufeld, T.P. AU - Cabreiro, F. AU - Partridge, L. TI - Fine-tuning autophagy maximises lifespan and is associated with changes in mitochondrial gene expression in Drosophila JF - PLOS GENETICS J2 - PLOS GENET VL - 16 PY - 2020 IS - 11 SN - 1553-7390 DO - 10.1371/journal.pgen.1009083 UR - https://m2.mtmt.hu/api/publication/31868486 ID - 31868486 N1 - Institute of Healthy Ageing, Research Department of Genetics, Evolution and Environment, University College London, London, United Kingdom UCL Cancer Institute, Paul O'Gorman Building, London, United Kingdom Max Planck Institute for Biology of Ageing, Cologne, Germany MRC London Institute of Medical Sciences, Imperial College London, Du Cane Road, London, United Kingdom EMBL European Bioinformatics Institute, Wellcome Trust Genome Campus, Hinxton, Cambridge, United Kingdom Section on Islet Cell and Regenerative Biology, Research Division, Joslin Diabetes Center, Boston, MA, United States Department of Genetics, Harvard Stem Cell Institute, Harvard Medical School, Boston, MA, United States Institute of Structural and Molecular Biology, University College London, London, United Kingdom LAGENBIO, Facultad de Veterinaria-IIS, IA2-CITA, CIBERNED, Universidad de Zaragoza, Zaragoza, Spain MRC Mitochondrial Biology Unit, Keith Peters Building, University of Cambridge, Cambridge, United Kingdom Department of Genetics, Cell Biology and Development, University of Minnesota, 321 Church St. SE, Minneapolis, MN, United States Institute of Immunology and Infection Research, University of Edinburgh, Charlotte, Edinburgh, United Kingdom Export Date: 12 February 2021 Correspondence Address: Bjedov, I.; Institute of Healthy Ageing, United Kingdom; email: i.bjedov@ucl.ac.uk Institute of Healthy Ageing, Research Department of Genetics, Evolution and Environment, University College London, London, United Kingdom UCL Cancer Institute, Paul O'Gorman Building, London, United Kingdom Max Planck Institute for Biology of Ageing, Cologne, Germany MRC London Institute of Medical Sciences, Imperial College London, Du Cane Road, London, United Kingdom EMBL European Bioinformatics Institute, Wellcome Trust Genome Campus, Hinxton, Cambridge, United Kingdom Section on Islet Cell and Regenerative Biology, Research Division, Joslin Diabetes Center, Boston, MA, United States Department of Genetics, Harvard Stem Cell Institute, Harvard Medical School, Boston, MA, United States Institute of Structural and Molecular Biology, University College London, London, United Kingdom LAGENBIO, Facultad de Veterinaria-IIS, IA2-CITA, CIBERNED, Universidad de Zaragoza, Zaragoza, Spain MRC Mitochondrial Biology Unit, Keith Peters Building, University of Cambridge, Cambridge, United Kingdom Department of Genetics, Cell Biology and Development, University of Minnesota, 321 Church St. SE, Minneapolis, MN, United States Institute of Immunology and Infection Research, University of Edinburgh, Charlotte, Edinburgh, United Kingdom Export Date: 14 February 2021 Correspondence Address: Bjedov, I.; Institute of Healthy Ageing, United Kingdom; email: i.bjedov@ucl.ac.uk Institute of Healthy Ageing, Research Department of Genetics, Evolution and Environment, University College London, London, United Kingdom UCL Cancer Institute, Paul O'Gorman Building, London, United Kingdom Max Planck Institute for Biology of Ageing, Cologne, Germany MRC London Institute of Medical Sciences, Imperial College London, Du Cane Road, London, United Kingdom EMBL European Bioinformatics Institute, Wellcome Trust Genome Campus, Hinxton, Cambridge, United Kingdom Section on Islet Cell and Regenerative Biology, Research Division, Joslin Diabetes Center, Boston, MA, United States Department of Genetics, Harvard Stem Cell Institute, Harvard Medical School, Boston, MA, United States Institute of Structural and Molecular Biology, University College London, London, United Kingdom LAGENBIO, Facultad de Veterinaria-IIS, IA2-CITA, CIBERNED, Universidad de Zaragoza, Zaragoza, Spain MRC Mitochondrial Biology Unit, Keith Peters Building, University of Cambridge, Cambridge, United Kingdom Department of Genetics, Cell Biology and Development, University of Minnesota, 321 Church St. SE, Minneapolis, MN, United States Institute of Immunology and Infection Research, University of Edinburgh, Charlotte, Edinburgh, United Kingdom Cited By :1 Export Date: 10 May 2021 Correspondence Address: Bjedov, I.; Institute of Healthy Ageing, United Kingdom; email: i.bjedov@ucl.ac.uk Institute of Healthy Ageing, Research Department of Genetics, Evolution and Environment, University College London, London, United Kingdom UCL Cancer Institute, Paul O'Gorman Building, London, United Kingdom Max Planck Institute for Biology of Ageing, Cologne, Germany MRC London Institute of Medical Sciences, Imperial College London, Du Cane Road, London, United Kingdom EMBL European Bioinformatics Institute, Wellcome Trust Genome Campus, Hinxton, Cambridge, United Kingdom Section on Islet Cell and Regenerative Biology, Research Division, Joslin Diabetes Center, Boston, MA, United States Department of Genetics, Harvard Stem Cell Institute, Harvard Medical School, Boston, MA, United States Institute of Structural and Molecular Biology, University College London, London, United Kingdom LAGENBIO, Facultad de Veterinaria-IIS, IA2-CITA, CIBERNED, Universidad de Zaragoza, Zaragoza, Spain MRC Mitochondrial Biology Unit, Keith Peters Building, University of Cambridge, Cambridge, United Kingdom Department of Genetics, Cell Biology and Development, University of Minnesota, 321 Church St. SE, Minneapolis, MN, United States Institute of Immunology and Infection Research, University of Edinburgh, Charlotte, Edinburgh, United Kingdom Cited By :1 Export Date: 11 May 2021 Correspondence Address: Bjedov, I.; Institute of Healthy Ageing, United Kingdom; email: i.bjedov@ucl.ac.uk Funding Agency and Grant Number: Research into Ageing (Age UK); Wellcome TrustWellcome TrustEuropean Commission; Max Planck SocietyMax Planck SocietyFoundation CELLEX; European Research Council Starting GrantEuropean Research Council (ERC); Cancer Research UKCancer Research UK; Bill Lyons foundation Funding text: This work was supported by Research into Ageing (Age UK), the Wellcome Trust and the Max Planck Society (L.P.). The work was also funded by European Research Council Starting Grant, Cancer Research UK and The Bill Lyons foundation (I.B.). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. AB - Increased cellular degradation by autophagy is a feature of many interventions that delay ageing. We report here that increased autophagy is necessary for reduced insulin-like signalling (IIS) to extend lifespan in Drosophila and is sufficient on its own to increase lifespan. We first established that the well-characterised lifespan extension associated with deletion of the insulin receptor substrate chico was completely abrogated by downregulation of the essential autophagy gene Atg5. We next directly induced autophagy by over-expressing the major autophagy kinase Atg1 and found that a mild increase in autophagy extended lifespan. Interestingly, strong Atg1 up-regulation was detrimental to lifespan. Transcriptomic and metabolomic approaches identified specific signatures mediated by varying levels of autophagy in flies. Transcriptional upregulation of mitochondrial-related genes was the signature most specifically associated with mild Atg1 upregulation and extended lifespan, whereas short-lived flies, possessing strong Atg1 overexpression, showed reduced mitochondrial metabolism and up-regulated immune system pathways. Increased proteasomal activity and reduced triacylglycerol levels were features shared by both moderate and high Atg1 overexpression conditions. These contrasting effects of autophagy on ageing and differential metabolic profiles highlight the importance of fine-tuning autophagy levels to achieve optimal healthspan and disease prevention. © 2020 Bjedov et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. LA - English DB - MTMT ER - TY - JOUR AU - Mondotte, Juan A AU - Saleh, Maria-Carla TI - Antiviral Immune Response and the Route of Infection in Drosophila melanogaster JF - ADVANCES IN VIRUS RESEARCH J2 - ADV VIRUS RES VL - 100 PY - 2018 SP - 247 EP - 278 PG - 32 SN - 0065-3527 DO - 10.1016/bs.aivir.2017.10.006 UR - https://m2.mtmt.hu/api/publication/27523506 ID - 27523506 LA - English DB - MTMT ER - TY - JOUR AU - Kari, Beáta AU - Csordás, Gábor AU - Honti, Viktor AU - Cinege, Gyöngyi Ilona AU - Williams, MJ AU - Andó, István AU - Kurucz, Judit Éva TI - The raspberry Gene Is Involved in the Regulation of the Cellular Immune Response in Drosophila melanogaster JF - PLOS ONE J2 - PLOS ONE VL - 11 PY - 2016 IS - 3 PG - 13 SN - 1932-6203 DO - 10.1371/journal.pone.0150910 UR - https://m2.mtmt.hu/api/publication/3045263 ID - 3045263 N1 - Biological Research Centre of Hungarian Academy of Sciences, Immunology Unit, Institute of Genetics, Szeged, Hungary Department of Neuroscience, Functional Pharmacology, Uppsala University, Uppsala, Sweden Cited By :6 Export Date: 14 February 2021 CODEN: POLNC AB - Drosophila is an extremely useful model organism for understanding how innate immune mechanisms defend against microbes and parasitoids. Large foreign objects trigger a potent cellular immune response in Drosophila larva. In the case of endoparasitoid wasp eggs, this response includes hemocyte proliferation, lamellocyte differentiation and eventual encapsulation of the egg. The encapsulation reaction involves the attachment and spreading of hemocytes around the egg, which requires cytoskeletal rearrangements, changes in adhesion properties and cell shape, as well as melanization of the capsule. Guanine nucleotide metabolism has an essential role in the regulation of pathways necessary for this encapsulation response. Here, we show that the Drosophila inosine 5'-monophosphate dehydrogenase (IMPDH), encoded by raspberry (ras), is centrally important for a proper cellular immune response against eggs from the parasitoid wasp Leptopilina boulardi. Notably, hemocyte attachment to the egg and subsequent melanization of the capsule are deficient in hypomorphic ras mutant larvae, which results in a compromised cellular immune response and increased survival of the parasitoid. LA - English DB - MTMT ER - TY - JOUR AU - Neyen, C AU - Bretscher, AJ AU - Binggeli, O AU - Lemaitre, B TI - Methods to study Drosophila immunity JF - METHODS J2 - METHODS VL - 68 PY - 2014 IS - 1 SP - 116 EP - 128 PG - 13 SN - 1046-2023 DO - 10.1016/j.ymeth.2014.02.023 UR - https://m2.mtmt.hu/api/publication/24356213 ID - 24356213 N1 - Cited By :59 Export Date: 31 January 2020 CODEN: MTHDE Correspondence Address: Neyen, C.; Global Health Institute, School of Life Sciences, Ecole Polytechnique Fédérale de Lausanne (EPFL), Station 19, 1015 Lausanne, Switzerland; email: claudine.neyen@epfl.ch LA - English DB - MTMT ER -