TY - JOUR AU - Jacomin, Anne-Claire AU - Gohel, Raksha AU - Hussain, Zunoon AU - Varga, Ágnes AU - Maruzs, Tamás AU - Eddison, Mark AU - Sica, Margaux AU - Jain, Ashish AU - Moffat, Kevin G AU - Johansen, Terje AU - Jenny, Andreas AU - Juhász, Gábor AU - Nezis, Ioannis P TI - Degradation of arouser by endosomal microautophagy is essential for adaptation to starvation in Drosophila. JF - LIFE SCIENCE ALLIANCE J2 - LIFE SCI ALLIANCE VL - 4 PY - 2021 IS - 2 SN - 2575-1077 DO - 10.26508/lsa.202000965 UR - https://m2.mtmt.hu/api/publication/31786473 ID - 31786473 N1 - Funding Agency and Grant Number: Biotechnology and Biological Sciences Research Council [BB/L006324/1, BB/P007856/1]; BBSRC [BB/L006324/1, BB/P007856/1] Funding Source: UKRI Funding text: We thank Dr J Bischof for sending the pUAST-attB plasmid and M Ward and A Torok for fly food preparation. We would like to acknowledge the contribution of the Warwickshire Private Hospital Proteomics Research Technology Platform, Gibbet Hill Road, University of Warwick, UK. The Bloomington Drosophila Stock Center contributed to this work by providing mutant and transgenic fly strains. We acknowledge Bestgene Inc for the injection and selection of transgenic flies. This work was supported by Biotechnology and Biological Sciences Research Council grants BB/L006324/1 and BB/P007856/1 awarded to IP Nezis. AB - Hunger drives food-seeking behaviour and controls adaptation of organisms to nutrient availability and energy stores. Lipids constitute an essential source of energy in the cell that can be mobilised during fasting by autophagy. Selective degradation of proteins by autophagy is made possible essentially by the presence of LIR and KFERQ-like motifs. Using in silico screening of Drosophila proteins that contain KFERQ-like motifs, we identified and characterized the adaptor protein Arouser, which functions to regulate fat storage and mobilisation and is essential during periods of food deprivation. We show that hypomorphic arouser mutants are not satiated, are more sensitive to food deprivation, and are more aggressive, suggesting an essential role for Arouser in the coordination of metabolism and food-related behaviour. Our analysis shows that Arouser functions in the fat body through nutrient-related signalling pathways and is degraded by endosomal microautophagy. Arouser degradation occurs during feeding conditions, whereas its stabilisation during non-feeding periods is essential for resistance to starvation and survival. In summary, our data describe a novel role for endosomal microautophagy in energy homeostasis, by the degradation of the signalling regulatory protein Arouser. LA - English DB - MTMT ER - TY - JOUR AU - Takáts, Szabolcs AU - Lévay, Luca AU - Boda, Attila AU - Tóth, Sarolta AU - Simon-Vecsei, Zsófia Judit AU - Rubics, András AU - Varga, Ágnes AU - Lippai, Mónika AU - Lőrincz, Péter AU - Glatz, Gábor AU - Juhász, Gábor TI - The Warburg Micro Syndrome-associated Rab3GAP-Rab18 module promotes autolysosome maturation through the Vps34 Complex I JF - FEBS JOURNAL J2 - FEBS J VL - 288 PY - 2021 IS - 1 SP - 190 EP - 211 PG - 22 SN - 1742-464X DO - 10.1111/febs.15313 UR - https://m2.mtmt.hu/api/publication/31279236 ID - 31279236 N1 - Funding Agency and Grant Number: Hungarian Academy of SciencesHungarian Academy of Sciences [LP-2014/2, PPD-003/2016, PPD-222/2018, BO/00652/17]; National Research, Development and Innovation Office of Hungary [GINOP-2.3.2-15-2016-00006, GINOP-2.3.2-15-2016-00032, K119842, KKP129797, KH125108, PD124594]; uNKP New National Excellence Program of the Ministry of Human Capacities of Hungary [uNKP-17-3-I-ELTE-27, uNKP-18-3-I-ELTE-314, uNKP-18-4-ELTE-409] Funding text: We thank Sarolta Palfia for the excellent technical assistance and colleagues and stock centers listed in the section for providing reagents. This work was supported by the Hungarian Academy of Sciences [LP-2014/2 to GJ, PPD-003/2016 to ST, PPD-222/2018 to PL, BO/00652/17 to ZSV.]; the National Research, Development and Innovation Office of Hungary [GINOP-2.3.2-15-2016-00006 and -00032, K119842, and KKP129797 to GJ, KH125108 to ST, PD124594 to ZSV]; and the uNKP New National Excellence Program of the Ministry of Human Capacities of Hungary (uNKP-17-3-I-ELTE-27 and uNKP-18-3-I-ELTE-314 to AB, uNKP-18-4-ELTE-409 to ZSV.). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. LA - English DB - MTMT ER - TY - JOUR AU - Lőrincz, Péter AU - Kenéz, Lili Anna AU - Tóth, Sarolta AU - Kiss, Viktória AU - Varga, Ágnes AU - Csizmadia, Tamás AU - Simon-Vecsei, Zsófia Judit AU - Juhász, Gábor TI - Vps8 overexpression inhibits HOPS-dependent trafficking routes by outcompeting Vps41/Lt JF - ELIFE J2 - ELIFE VL - 8 PY - 2019 PG - 25 SN - 2050-084X DO - 10.7554/eLife.45631 UR - https://m2.mtmt.hu/api/publication/30715075 ID - 30715075 N1 - Funding Agency and Grant Number: Magyar Tudomanyos Akademia [LP -2014/2, PPD-222/2018, BO/00652/17]; National Research Development and Innovation OfficeNational Research, Development & Innovation Office (NRDIO) - Hungary [GINOP-2.3.2-15-2016-00006, GINOP-2.3.2-15-2016-00032, K119842, PD124594]; Ministry of Human Capacities [UNKP-18-2-IIELTE-32, UNKP-18-4-ELTE-409] Funding text: Magyar Tudomanyos Akade-mia LP -2014/2 Gabor Juhasz; Magyar Tudomanyos Akade-mia PPD-222/2018 Peter Lorincz; Magyar Tudomanyos Akade-mia BO/00652/17 ZsOfia Simon-Vecsei; National Research Development and Innovation Office GINOP-2.3.2-15-2016-00006 Gabor Juhasz; National Research Development and Innovation Office GINOP-2.3.2-15-2016-00032 Gabor Juhasz; National Research Development and Innovation Office K119842 Gabor Juhasz; National Research Development and Innovation Office PD124594 Zsofia Simon-Vecsei; Ministry of Human Capacities UNKP-18-2-IIELTE-32 Lili Anna Kenez; Ministry of Human Capacities UNKP-18-4-ELTE-409 Zsofia Simon-Vecsei; The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication. LA - English DB - MTMT ER - TY - JOUR AU - Lőrincz, Péter AU - Lakatos, Zsolt AU - Varga, Ágnes AU - Maruzs, Tamás AU - Simon-Vecsei, Zsófia Judit AU - Darula, Zsuzsanna AU - Benkő, Péter AU - Csordás, Gábor AU - Lippai, Mónika AU - Andó, István AU - Hegedűs, Krisztina AU - Medzihradszky F., Katalin AU - Takáts, Szabolcs AU - Juhász, Gábor TI - MiniCORVET is a Vps8-containing early endosomal tether in Drosophila JF - ELIFE J2 - ELIFE VL - 5 PY - 2016 PG - 27 SN - 2050-084X DO - 10.7554/eLife.14226 UR - https://m2.mtmt.hu/api/publication/30901168 ID - 30901168 N1 - Cited By :33 Export Date: 30 June 2022 AB - Yeast studies identified two heterohexameric tethering complexes, which consist of 4 shared (Vps11, Vps16, Vps18 and Vps33) and 2 specific subunits: Vps3 and Vps8 (CORVET) versus Vps39 and Vps41 (HOPS). CORVET is an early and HOPS is a late endosomal tether. The function of HOPS is well known in animal cells, while CORVET is poorly characterized. Here we show that Drosophila Vps8 is highly expressed in hemocytes and nephrocytes, and localizes to early endosomes despite the lack of a clear Vps3 homolog. We find that Vps8 forms a complex and acts together with Vps16A, Dor/Vps18 and Car/Vps33A, and loss of any of these proteins leads to fragmentation of endosomes. Surprisingly, Vps11 deletion causes enlargement of endosomes, similar to loss of the HOPS-specific subunits Vps39 and Lt/Nps41. We thus identify a 4 subunit-containing miniCORVET complex as an unconventional early endosomal tether in Drosophila. LA - English DB - MTMT ER - TY - JOUR AU - Takáts, Szabolcs AU - Varga, Ágnes AU - Pircs, Karolina Milena AU - Juhász, Gábor TI - Loss of Drosophila Vps16A enhances autophagosome formation through reduced TOR activity. JF - AUTOPHAGY J2 - AUTOPHAGY VL - 11 PY - 2015 IS - 8 SP - 1209 EP - 1215 PG - 7 SN - 1554-8627 DO - 10.1080/15548627.2015.1059559 UR - https://m2.mtmt.hu/api/publication/2909898 ID - 2909898 N1 - Megjegyzés-25134925 N1 Funding Details: 087518/Z/08/Z, Wellcome Trust Journal Article; Research Support, Non-U.S. Gov't Department of Anatomy, Cell and Developmental Biology, Eötvös Lorand University, Budapest, Hungary Momentum Drosophila Autophagy Research Group, Institute of Genetics, Biological Research Center, Hungarian Academy of Sciences, Szeged, Hungary Molecular Neurogenetics, Lund University, Sölvegatan, Sweden Cited By :6 Export Date: 4 May 2021 Correspondence Address: Juhász, G.; Department of Anatomy, Hungary; email: szmrt@elte.hu Funding Agency and Grant Number: Wellcome TrustWellcome TrustEuropean Commission [087518/Z/08/Z]; Hungarian Scientific Research FundOrszagos Tudomanyos Kutatasi Alapprogramok (OTKA) [OTKA K83509] Funding text: We thank the Wellcome Trust (087518/Z/08/Z) and the Hungarian Scientific Research Fund (OTKA K83509) for support. Department of Anatomy, Cell and Developmental Biology, Eötvös Lorand University, Budapest, Hungary Momentum Drosophila Autophagy Research Group, Institute of Genetics, Biological Research Center, Hungarian Academy of Sciences, Szeged, Hungary Molecular Neurogenetics, Lund University, Sölvegatan, Sweden Cited By :6 Export Date: 23 September 2021 Correspondence Address: Juhász, G.; Department of Anatomy, Hungary; email: szmrt@elte.hu AB - The HOPS tethering complex facilitates autophagosome-lysosome fusion by binding to Syntaxin 17, the autophagosomal SNARE. Here we show that loss of the core HOPS complex subunit Vps16A enhances autophagosome formation and slows down Drosophila development. Mechanistically, Tor kinase is less active in Vps16A mutants likely due to impaired endocytic and biosynthetic transport to the lysosome, a site of its activation. Tor reactivation by overexpression of Rheb suppresses autophagosome formation and restores growth and developmental timing in these animals. Thus, Vps16A reduces autophagosome numbers both by indirectly restricting their formation rate and by directly promoting their clearance. In contrast, the loss of Syx17/Syntaxin 17 blocks autophagic flux without affecting the induction step in Drosophila. LA - English DB - MTMT ER - TY - JOUR AU - Nagy, Péter AU - Varga, Ágnes AU - Kovács, Attila Lajos AU - Takáts, Szabolcs AU - Juhász, Gábor TI - How and why to study autophagy in Drosophila:It's more than just a garbage chute. JF - METHODS J2 - METHODS VL - 75 PY - 2015 SP - 151 EP - 161 PG - 11 SN - 1046-2023 DO - 10.1016/j.ymeth.2014.11.016 UR - https://m2.mtmt.hu/api/publication/2789675 ID - 2789675 N1 - Funding Agency and Grant Number: Hungarian Scientific Research FundOrszagos Tudomanyos Kutatasi Alapprogramok (OTKA) [OTKA K83509]; Wellcome TrustWellcome TrustEuropean Commission [087518/Z/08/Z] Funding text: The authors would like to thank all members of the Juhasz lab, who contributed to the development and testing of some of the tools described in this review. The collection of results presented in this paper has been supported by grants from the Hungarian Scientific Research Fund (OTKA K83509) and the Wellcome Trust (087518/Z/08/Z) to GJ. AB - During the catabolic process of autophagy, cytoplasmic material is transported to the lysosome for degradation and recycling. This way, autophagy contributes to the homeodynamic turnover of proteins, lipids, nucleic acids, glycogen, and even whole organelles. Autophagic activity is increased by adverse conditions such as nutrient limitation, growth factor withdrawal and oxidative stress, and it generally protects cells and organisms to promote their survival. Misregulation of autophagy is likely involved in numerous human pathologies including aging, cancer, infections and neurodegeneration, so its biomedical relevance explains the still growing interest in this field. Here we discuss the different microscopy-based, biochemical and genetic methods currently available to study autophagy in various tissues of the popular model Drosophila. We show examples for results obtained in different assays, explain how to interpret these with regard to autophagic activity, and how to find out which step of autophagy a given gene product is involved in. LA - English DB - MTMT ER - TY - JOUR AU - Takáts, Szabolcs AU - Pircs, Karolina Milena AU - Nagy, Péter AU - Varga, Ágnes AU - Kárpáti, Manuéla AU - Hegedűs, Krisztina AU - Kramer, H AU - Kovács, Attila Lajos AU - Sass, Miklós AU - Juhász, Gábor TI - Interaction of the HOPS complex with Syntaxin 17 mediates autophagosome clearance in Drosophila JF - MOLECULAR BIOLOGY OF THE CELL J2 - MOL BIOL CELL VL - 25 PY - 2014 IS - 8 SP - 1338 EP - 1354 PG - 17 SN - 1059-1524 DO - 10.1091/mbc.E13-08-0449 UR - https://m2.mtmt.hu/api/publication/2527687 ID - 2527687 N1 - Department of Anatomy, Cell and Developmental Biology, Eötvös Loránd University, Pazmany s. 1/C, H-1117 Budapest, Hungary Department of Neuroscience, Department of Cell Biology, University of Texas Southwestern Medical School, Dallas, TX, United States Cited By :138 Export Date: 4 May 2021 CODEN: MBCEE Correspondence Address: Juhász, G.; Department of Anatomy, Cell and Developmental Biology, Eötvös Loránd University, Pazmany s. 1/C, H-1117 Budapest, Hungary; email: szmrt@elte.hu LA - English DB - MTMT ER - TY - JOUR AU - Nagy, Péter AU - Hegedűs, Krisztina AU - Pircs, Karolina Milena AU - Varga, Ágnes AU - Juhász, Gábor TI - Different effects of Atg2 and Atg18 mutations on Atg8a and Atg9 trafficking during starvation in Drosophila. JF - FEBS LETTERS J2 - FEBS LETT VL - 588 PY - 2014 IS - 3 SP - 408 EP - 413 PG - 6 SN - 0014-5793 DO - 10.1016/j.febslet.2013.12.012 UR - https://m2.mtmt.hu/api/publication/2502658 ID - 2502658 N1 - Cited By :29 Export Date: 4 May 2021 CODEN: FEBLA Correspondence Address: Juhász, G.; Department of Anatomy, Cell and Developmental Biology, Pázmány s. 1/C. 6.520, Budapest H-1117, Hungary; email: szmrt@elte.hu AB - The Atg2-Atg18 complex acts in parallel to Atg8 and regulates Atg9 recycling from phagophore assembly site (PAS) during autophagy in yeast. Here we show that in Drosophila, both Atg9 and Atg18 are required for Atg8a puncta formation, unlike Atg2. Selective autophagic degradation of ubiquitinated proteins is mediated by Ref(2)P/p62. The transmembrane protein Atg9 accumulates on refractory to Sigma P (Ref(2)P) aggregates in Atg7, Atg8a and Atg2 mutants. No accumulation of Atg9 is seen on Ref(2)P in cells lacking Atg18 or Vps34 lipid kinase function, while the Atg1 complex subunit FIP200 is recruited. The simultaneous interaction of Atg18 with both Atg9 and Ref(2)P raises the possibility that Atg18 may facilitate selective degradation of ubiquitinated protein aggregates by autophagy. LA - English DB - MTMT ER - TY - JOUR AU - Nagy, Péter AU - Kárpáti, Manuéla AU - Varga, Ágnes AU - Pircs, Karolina Milena AU - Venkei, Z AU - Takáts, Szabolcs AU - Varga, Kata AU - Érdi, Balázs AU - Hegedűs, Krisztina AU - Juhász, Gábor TI - Atg17/FIP200 localizes to perilysosomal Ref(2)P aggregates and promotes autophagy by activation of Atg1 in Drosophila JF - AUTOPHAGY J2 - AUTOPHAGY VL - 10 PY - 2014 IS - 3 SP - 453 EP - 467 PG - 15 SN - 1554-8627 DO - 10.4161/auto.27442 UR - https://m2.mtmt.hu/api/publication/2502657 ID - 2502657 N1 - Megjegyzés-23823594 Megjegyzés-23823728 Megjegyzés-23823755 Megjegyzés-23823799 Megjegyzés-23823938 Megjegyzés-24192952 Megjegyzés-24192958 Department of Anatomy, Cell and Developmental Biology, Eötvös Loránd University, Budapest, Hungary Center for Stem Cell Biology, Life Sciences Institute, University of Michigan, Ann Arbor, MI, United States IMP-Research Institute of Molecular Pathology, Vienna, Austria Cited By :49 Export Date: 4 May 2021 Correspondence Address: Juhász, G.; Department of Anatomy, , Budapest, Hungary; email: szmrt@elte.hu AB - Phagophore-derived autophagosomes deliver cytoplasmic material to lysosomes for degradation and reuse. Autophagy mediated by the incompletely characterized actions of Atg proteins is involved in numerous physiological and pathological settings including stress resistance, immunity, aging, cancer, and neurodegenerative diseases. Here we characterized Atg17/FIP200, the Drosophila ortholog of mammalian RB1CC1/FIP200, a proposed functional equivalent of yeast Atg17. Atg17 disruption inhibits basal, starvation-induced and developmental autophagy, and interferes with the programmed elimination of larval salivary glands and midgut during metamorphosis. Upon starvation, Atg17-positive structures appear at aggregates of the selective cargo Ref(2)P/p62 near lysosomes. This location may be similar to the perivacuolar PAS (phagophore assembly site) described in yeast. Drosophila Atg17 is a member of the Atg1 kinase complex as in mammals, and we showed that it binds to the other subunits including Atg1, Atg13 and Atg101 (C12orf44 in humans, 9430023L20Rik in mice and RGD1359310 in rats). Atg17 is required for the kinase activity of endogenous Atg1 in vivo, as loss of Atg17 prevents the Atg1-dependent shift of endogenous Atg13 to hyperphosphorylated forms, and also blocks punctate Atg1 localization during starvation. Finally, we found that Atg1 overexpression induces autophagy and reduces cell size in Atg17-null mutant fat body cells, and that overexpression of Atg17 promotes endogenous Atg13 phosphorylation and enhances autophagy in an Atg1-dependent manner in the fat body. We propose a model according to which the relative activity of Atg1, estimated by the ratio of hyper- to hypophosphorylated Atg13, contributes to setting low (basal) vs. high (starvation-induced) autophagy levels in Drosophila. LA - English DB - MTMT ER - TY - CHAP AU - Hegedűs, Krisztina AU - Nagy, Péter AU - Varga, Ágnes AU - Pircs, Karolina Milena AU - Varga, Kata AU - Takáts, Szabolcs AU - Juhász, Gábor ED - Hohol, R ED - Heiszler, Zs TI - THE SELECTIVE AUTOPHAGY CARGO P62 FACILITATES AUTOPHAGOSOME FORMATION BY BINDING MULTIPLE ATG PROTEINS IN DROSOPHILA T2 - Hungarian Molecular Life Sciences 2013 PB - Diamond Congress Kft. CY - Budapest SN - 9786155270024 PY - 2013 SP - 192 PG - 289 UR - https://m2.mtmt.hu/api/publication/2855146 ID - 2855146 N1 - Besorolás: Konferenciakötet Város: Siófok; Balatonszéplak Ország: Magyarország Befejező dátum: 2013-04-07 ISBN: 978-615-5270-02-4 Kiadás helye: Budapest Kezdő dátum: 2013-04-05 Kötet cím: Hungarian Molecular Life Sciences 2013 PROGRAMME & BOOK OF ABSTRACTS # Cikk azonosító vagy Kezdő oldal ismeretlen LA - English DB - MTMT ER -