@article{MTMT:31786473, title = {Degradation of arouser by endosomal microautophagy is essential for adaptation to starvation in Drosophila.}, url = {https://m2.mtmt.hu/api/publication/31786473}, author = {Jacomin, Anne-Claire and Gohel, Raksha and Hussain, Zunoon and Varga, Ágnes and Maruzs, Tamás and Eddison, Mark and Sica, Margaux and Jain, Ashish and Moffat, Kevin G and Johansen, Terje and Jenny, Andreas and Juhász, Gábor and Nezis, Ioannis P}, doi = {10.26508/lsa.202000965}, journal-iso = {LIFE SCI ALLIANCE}, journal = {LIFE SCIENCE ALLIANCE}, volume = {4}, unique-id = {31786473}, abstract = {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.}, year = {2021}, eissn = {2575-1077}, orcid-numbers = {Maruzs, Tamás/0000-0001-8142-3221; Juhász, Gábor/0000-0001-8548-8874} } @article{MTMT:31279236, title = {The Warburg Micro Syndrome-associated Rab3GAP-Rab18 module promotes autolysosome maturation through the Vps34 Complex I}, url = {https://m2.mtmt.hu/api/publication/31279236}, author = {Takáts, Szabolcs and Lévay, Luca and Boda, Attila and Tóth, Sarolta and Simon-Vecsei, Zsófia Judit and Rubics, András and Varga, Ágnes and Lippai, Mónika and Lőrincz, Péter and Glatz, Gábor and Juhász, Gábor}, doi = {10.1111/febs.15313}, journal-iso = {FEBS J}, journal = {FEBS JOURNAL}, volume = {288}, unique-id = {31279236}, issn = {1742-464X}, year = {2021}, eissn = {1742-4658}, pages = {190-211}, orcid-numbers = {Takáts, Szabolcs/0000-0003-2139-7740; Boda, Attila/0000-0003-1811-8595; Tóth, Sarolta/0000-0002-0341-7675; Simon-Vecsei, Zsófia Judit/0000-0001-7909-4895; Lippai, Mónika/0000-0002-7307-4233; Lőrincz, Péter/0000-0001-7374-667X; Juhász, Gábor/0000-0001-8548-8874} } @article{MTMT:30715075, title = {Vps8 overexpression inhibits HOPS-dependent trafficking routes by outcompeting Vps41/Lt}, url = {https://m2.mtmt.hu/api/publication/30715075}, author = {Lőrincz, Péter and Kenéz, Lili Anna and Tóth, Sarolta and Kiss, Viktória and Varga, Ágnes and Csizmadia, Tamás and Simon-Vecsei, Zsófia Judit and Juhász, Gábor}, doi = {10.7554/eLife.45631}, journal-iso = {ELIFE}, journal = {ELIFE}, volume = {8}, unique-id = {30715075}, issn = {2050-084X}, year = {2019}, eissn = {2050-084X}, orcid-numbers = {Lőrincz, Péter/0000-0001-7374-667X; Tóth, Sarolta/0000-0002-0341-7675; Csizmadia, Tamás/0000-0002-2098-9165; Simon-Vecsei, Zsófia Judit/0000-0001-7909-4895; Juhász, Gábor/0000-0001-8548-8874} } @article{MTMT:30901168, title = {MiniCORVET is a Vps8-containing early endosomal tether in Drosophila}, url = {https://m2.mtmt.hu/api/publication/30901168}, author = {Lőrincz, Péter and Lakatos, Zsolt and Varga, Ágnes and Maruzs, Tamás and Simon-Vecsei, Zsófia Judit and Darula, Zsuzsanna and Benkő, Péter and Csordás, Gábor and Lippai, Mónika and Andó, István and Hegedűs, Krisztina and Medzihradszky F., Katalin and Takáts, Szabolcs and Juhász, Gábor}, doi = {10.7554/eLife.14226}, journal-iso = {ELIFE}, journal = {ELIFE}, volume = {5}, unique-id = {30901168}, issn = {2050-084X}, abstract = {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.}, year = {2016}, eissn = {2050-084X}, orcid-numbers = {Lőrincz, Péter/0000-0001-7374-667X; Lakatos, Zsolt/0000-0003-1900-3167; Maruzs, Tamás/0000-0001-8142-3221; Simon-Vecsei, Zsófia Judit/0000-0001-7909-4895; Benkő, Péter/0000-0002-2050-7509; Csordás, Gábor/0000-0001-6871-6839; Lippai, Mónika/0000-0002-7307-4233; Andó, István/0000-0002-4648-9396; Takáts, Szabolcs/0000-0003-2139-7740; Juhász, Gábor/0000-0001-8548-8874} } @article{MTMT:2909898, title = {Loss of Drosophila Vps16A enhances autophagosome formation through reduced TOR activity.}, url = {https://m2.mtmt.hu/api/publication/2909898}, author = {Takáts, Szabolcs and Varga, Ágnes and Pircs, Karolina Milena and Juhász, Gábor}, doi = {10.1080/15548627.2015.1059559}, journal-iso = {AUTOPHAGY}, journal = {AUTOPHAGY}, volume = {11}, unique-id = {2909898}, issn = {1554-8627}, abstract = {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.}, year = {2015}, eissn = {1554-8635}, pages = {1209-1215}, orcid-numbers = {Takáts, Szabolcs/0000-0003-2139-7740; Pircs, Karolina Milena/0000-0001-8281-4785; Juhász, Gábor/0000-0001-8548-8874} } @article{MTMT:2789675, title = {How and why to study autophagy in Drosophila:It's more than just a garbage chute.}, url = {https://m2.mtmt.hu/api/publication/2789675}, author = {Nagy, Péter and Varga, Ágnes and Kovács, Attila Lajos and Takáts, Szabolcs and Juhász, Gábor}, doi = {10.1016/j.ymeth.2014.11.016}, journal-iso = {METHODS}, journal = {METHODS}, volume = {75}, unique-id = {2789675}, issn = {1046-2023}, abstract = {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.}, year = {2015}, eissn = {1095-9130}, pages = {151-161}, orcid-numbers = {Nagy, Péter/0000-0002-5053-0646; Takáts, Szabolcs/0000-0003-2139-7740; Juhász, Gábor/0000-0001-8548-8874} } @article{MTMT:2527687, title = {Interaction of the HOPS complex with Syntaxin 17 mediates autophagosome clearance in Drosophila}, url = {https://m2.mtmt.hu/api/publication/2527687}, author = {Takáts, Szabolcs and Pircs, Karolina Milena and Nagy, Péter and Varga, Ágnes and Kárpáti, Manuéla and Hegedűs, Krisztina and Kramer, H and Kovács, Attila Lajos and Sass, Miklós and Juhász, Gábor}, doi = {10.1091/mbc.E13-08-0449}, journal-iso = {MOL BIOL CELL}, journal = {MOLECULAR BIOLOGY OF THE CELL}, volume = {25}, unique-id = {2527687}, issn = {1059-1524}, year = {2014}, eissn = {1939-4586}, pages = {1338-1354}, orcid-numbers = {Takáts, Szabolcs/0000-0003-2139-7740; Pircs, Karolina Milena/0000-0001-8281-4785; Nagy, Péter/0000-0002-5053-0646; Juhász, Gábor/0000-0001-8548-8874} } @article{MTMT:2502658, title = {Different effects of Atg2 and Atg18 mutations on Atg8a and Atg9 trafficking during starvation in Drosophila.}, url = {https://m2.mtmt.hu/api/publication/2502658}, author = {Nagy, Péter and Hegedűs, Krisztina and Pircs, Karolina Milena and Varga, Ágnes and Juhász, Gábor}, doi = {10.1016/j.febslet.2013.12.012}, journal-iso = {FEBS LETT}, journal = {FEBS LETTERS}, volume = {588}, unique-id = {2502658}, issn = {0014-5793}, abstract = {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.}, year = {2014}, eissn = {1873-3468}, pages = {408-413}, orcid-numbers = {Nagy, Péter/0000-0002-5053-0646; Pircs, Karolina Milena/0000-0001-8281-4785; Juhász, Gábor/0000-0001-8548-8874} } @article{MTMT:2502657, title = {Atg17/FIP200 localizes to perilysosomal Ref(2)P aggregates and promotes autophagy by activation of Atg1 in Drosophila}, url = {https://m2.mtmt.hu/api/publication/2502657}, author = {Nagy, Péter and Kárpáti, Manuéla and Varga, Ágnes and Pircs, Karolina Milena and Venkei, Z and Takáts, Szabolcs and Varga, Kata and Érdi, Balázs and Hegedűs, Krisztina and Juhász, Gábor}, doi = {10.4161/auto.27442}, journal-iso = {AUTOPHAGY}, journal = {AUTOPHAGY}, volume = {10}, unique-id = {2502657}, issn = {1554-8627}, abstract = {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.}, year = {2014}, eissn = {1554-8635}, pages = {453-467}, orcid-numbers = {Nagy, Péter/0000-0002-5053-0646; Pircs, Karolina Milena/0000-0001-8281-4785; Takáts, Szabolcs/0000-0003-2139-7740; Juhász, Gábor/0000-0001-8548-8874} } @{MTMT:2855146, title = {THE SELECTIVE AUTOPHAGY CARGO P62 FACILITATES AUTOPHAGOSOME FORMATION BY BINDING MULTIPLE ATG PROTEINS IN DROSOPHILA}, url = {https://m2.mtmt.hu/api/publication/2855146}, author = {Hegedűs, Krisztina and Nagy, Péter and Varga, Ágnes and Pircs, Karolina Milena and Varga, Kata and Takáts, Szabolcs and Juhász, Gábor}, booktitle = {Hungarian Molecular Life Sciences 2013}, unique-id = {2855146}, year = {2013}, pages = {192-481}, orcid-numbers = {Nagy, Péter/0000-0002-5053-0646; Pircs, Karolina Milena/0000-0001-8281-4785; Takáts, Szabolcs/0000-0003-2139-7740; Juhász, Gábor/0000-0001-8548-8874} }