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 - Hotzi, Bernadette AU - Kosztelnik, Mónika AU - Hargitai, Balázs AU - Vellainé Takács, Krisztina AU - Barna, János AU - Bördén, Ka AU - Málnási Csizmadia, András AU - Lippai, Mónika AU - Ortutay, Csaba Péter AU - Bacquet, C AU - Pasparaki, A AU - Arányi, Tamás AU - Tavernarakis, N AU - Vellai, Tibor TI - Sex-specific regulation of aging in Caenorhabditis elegans JF - AGING CELL J2 - AGING CELL VL - 17 PY - 2018 IS - 3 PG - 15 SN - 1474-9718 DO - 10.1111/acel.12724 UR - https://m2.mtmt.hu/api/publication/3346802 ID - 3346802 N1 - Megjegyzés-27443098 N1 Funding details: 01062 N1 Funding details: K109349, OTKA, Országos Tudományos Kutatási Alapprogramok N1 Funding details: VEKOP-2.3.2-16-2017-00014, MTA, Magyar Tudományos Akadémia N1 Funding details: K100638, MTA, Magyar Tudományos Akadémia N1 Funding details: ERC, European Research Council N1 Funding details: OTKA, Országos Tudományos Kutatási Alapprogramok N1 Funding text: This work was supported by the OTKA (Hungarian Scientific Research Fund) grant K109349, MTA-ELTE Genetics Research Group (01062), and MEDinPROT Protein Science Research Synergy Program (provided by the Hungarian Academy of Sciences) to T.V., by the OTKA grant K100638 to T.A., the VEKOP excellence grant (VEKOP-2.3.2-16-2017-00014) to T.V., and the Advanced Investigator ERC grant “NeuronAge” to N.T. The authors thank David Zar-kower for providing tra-1 cDNA. Megjegyzés-27411383 Besorolás Név: JOUR idéző Cikk azonos: e12724 idéző Cím: Sex-specific regulation of aging in Caenorhabditis elegans idéző Cím: Aging Cell idéző Folyóirat/Könyv cím/Szabadalmi szám: Aging Cell idéző Kötet: 17 Jelleg Műfaj: JOUR AB - A fascinating aspect of sexual dimorphism in various animal species is that the two sexes differ substantially in lifespan. In humans, for example, women's life expectancy exceeds that of men by 3-7 years. Whether this trait can be attributed to dissimilar lifestyles or genetic (regulatory) factors remains to be elucidated. Herein, we demonstrate that in the nematode Caenorhabditis elegans, the significantly longer lifespan of hermaphrodites-which are essentially females capable of sperm production-over males is established by TRA-1, the terminal effector of the sex-determination pathway. This transcription factor directly controls the expression of daf-16/FOXO, which functions as a major target of insulin/IGF-1 signaling (IIS) and key modulator of aging across diverse animal phyla. TRA-1 extends hermaphrodite lifespan through promoting daf-16 activity. Furthermore, TRA-1 also influences reproductive growth in a DAF-16-dependent manner. Thus, the sex-determination machinery is an important regulator of IIS in this organism. These findings provide a mechanistic insight into how longevity and development are specified unequally in the two genders. As TRA-1 is orthologous to mammalian GLI (glioma-associated) proteins, a similar sex-specific mechanism may also operate in humans to determine lifespan. © 2018 The Anatomical Society and John Wiley & Sons Ltd. LA - English DB - MTMT ER - TY - JOUR AU - Nagy, Péter AU - Szatmári, Zsuzsanna AU - Sándor, Gyöngyvér Orsolya AU - Lippai, Mónika AU - Hegedűs, Krisztina AU - Juhász, Gábor TI - Drosophila Atg16 promotes enteroendocrine cell differentiation via regulation of intestinal Slit/Robo signaling. JF - DEVELOPMENT J2 - DEVELOPMENT VL - 144 PY - 2017 IS - 21 SP - 3990 EP - 4001 PG - 12 SN - 0950-1991 DO - 10.1242/dev.147033 UR - https://m2.mtmt.hu/api/publication/3278744 ID - 3278744 N1 - These authors contributed equally to this work: Péter Nagy, Zsuzsanna Szatmári AB - Genetic variations of Atg16L1, Slit and Rab19 predispose to the development of inflammatory bowel disease (IBD), but the relationship of these mutations is unclear. Here we show that in Drosophila guts lacking the WD40 domain of Atg16, pre-enteroendocrine cells (pre-EEs) accumulate that fail to differentiate into properly functioning secretory EEs. Mechanistically, loss of Atg16 or its binding partner Rab19 impairs Slit production, which normally inhibits EE generation by activating Robo signaling in stem cells. Importantly, loss of Atg16 or decreased Slit/Robo signaling trigger an intestinal inflammatory response. Surprisingly, analysis of Rab19 and domain-specific Atg16 mutants indicates that their stem cell niche regulatory function is independent of autophagy. Our study reveals how mutations in these different genes may contribute to IBD. LA - English DB - MTMT ER - TY - JOUR AU - Lippai, Mónika AU - Szatmári, Zsuzsanna TI - Autophagy—from molecular mechanisms to clinical relevance JF - CELL BIOLOGY AND TOXICOLOGY J2 - CELL BIOL TOXICOL VL - 33 PY - 2017 IS - 2 SP - 145 EP - 168 PG - 24 SN - 0742-2091 DO - 10.1007/s10565-016-9374-5 UR - https://m2.mtmt.hu/api/publication/3158690 ID - 3158690 N1 - Cited By :52 Export Date: 21 September 2022 CODEN: CBTOE Correspondence Address: Szatmári, Z.; Department of Anatomy, Pázmány Péter stny. 1/C, Hungary; email: zsuzs.szatmari@gmail.com AB - Autophagy is a lysosomal degradation pathway of eukaryotic cells that is highly conserved from yeast to mammals. During this process, cooperating protein complexes are recruited in a hierarchic order to the phagophore assembly site (PAS) to mediate the elongation and closure of double-membrane vesicles called autophagosomes, which sequester cytosolic components and deliver their content to the endolysosomal system for degradation. As a major cytoprotective mechanism, autophagy plays a key role in the stress response against nutrient starvation, hypoxia, and infections. Although numerous studies reported that impaired function of core autophagy proteins also contributes to the development and progression of various human diseases such as neurodegenerative disorders, cardiovascular and muscle diseases, infections, and different types of cancer, the function of this process in human diseases remains unclear. Evidence often suggests a controversial role for autophagy in the pathomechanisms of these severe disorders. Here, we provide an overview of the molecular mechanisms of autophagy and summarize the recent advances on its function in human health and disease. © 2016 Springer Science+Business Media Dordrecht 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 - BOOK AU - Csikós, György AU - Csizmadia, Tamás AU - Csörgő, Tibor AU - Kárpáti, Manuéla AU - Kis, Viktor AU - Dr. Kovács, Attila AU - Molnár, Kinga AU - Pálfia, Zsolt ED - Lippai, Mónika TI - Állatszervezettani Gyakorlatok ET - 0 PB - ELTE Természettudományi Kar CY - Budapest PY - 2015 SP - 221 UR - https://m2.mtmt.hu/api/publication/3165682 ID - 3165682 LA - Hungarian DB - MTMT ER - TY - JOUR AU - Kis, Viktor AU - Barti, Benjámin AU - Lippai, Mónika AU - Sass, Miklós TI - Specialized Cortex Glial Cells Accumulate Lipid Droplets in Drosophila melanogaster JF - PLOS ONE J2 - PLOS ONE VL - 10 PY - 2015 IS - 7 PG - 19 SN - 1932-6203 DO - 10.1371/journal.pone.0131250 UR - https://m2.mtmt.hu/api/publication/2941631 ID - 2941631 AB - Lipid droplets (LDs) are common organelles of the majority of eukaryotic cell types. Their biological significance has been extensively studied in mammalian liver cells and white adipose tissue. Although the central nervous system contains the highest relative amount and the largest number of different lipid species, neither the spatial nor the temporal distribution of LDs has been described. In this study, we used the brain of the fruitfly, Drosophila melanogaster, to investigate the neuroanatomy of LDs. We demonstrated that LDs are exclusively localised in glial cells but not in neurons in the larval nervous system. We showed that the brain's LD pool, rather than being constant, changes dynamically during development and reaches its highest value at the beginning of metamorphosis. LDs are particularly enriched in cortex glial cells located close to the brain surface. These specialized superficial cortex glial cells contain the highest amount of LDs among glial cell types and encapsulate neuroblasts and their daughter cells. Superficial cortex glial cells, combined with subperineurial glial cells, express the Drosophila fatty acid binding protein (Dfabp), as we have demonstrated through light-and electron microscopic immunocytochemistry. To the best of our best knowledge this is the first study that describes LD neuroanatomy in the Drosophila larval brain. LA - English DB - MTMT ER - TY - JOUR AU - Lippai, Mónika AU - Lőw, Péter TI - The Role of the Selective Adaptor p62 and Ubiquitin-Like Proteins in Autophagy. JF - BIOMED RESEARCH INTERNATIONAL J2 - BIOMED RES INT VL - 2014 PY - 2014 PG - 11 SN - 2314-6133 DO - 10.1155/2014/832704 UR - https://m2.mtmt.hu/api/publication/2708962 ID - 2708962 N1 - Cited By :224 Export Date: 21 September 2022 Correspondence Address: Low, P.; Department of Anatomy, Cell and Developmental Biology, Eötvös Loránd University, Pazmany Peter setany 1/C, Budapest 1117, Hungary; email: peter.low@ttk.elte.hu AB - The ubiquitin-proteasome system and autophagy were long viewed as independent, parallel degradation systems with no point of intersection. By now we know that these degradation pathways share certain substrates and regulatory molecules and show coordinated and compensatory function. Two ubiquitin-like protein conjugation pathways were discovered that are required for autophagosome biogenesis: the Atg12-Atg5-Atg16 and Atg8 systems. Autophagy has been considered to be essentially a nonselective process, but it turned out to be at least partially selective. Selective substrates of autophagy include damaged mitochondria, intracellular pathogens, and even a subset of cytosolic proteins with the help of ubiquitin-binding autophagic adaptors, such as p62/SQSTM1, NBR1, NDP52, and Optineurin. These proteins selectively recognize autophagic cargo and mediate its engulfment into autophagosomes by binding to the small ubiquitin-like modifiers that belong to the Atg8/LC3 family. LA - English DB - MTMT ER - TY - JOUR AU - Szatmári, Zsuzsanna AU - Kis, Viktor AU - Lippai, Mónika AU - Hegedűs, Krisztina AU - Faragó, Tamás AU - Lőrincz, Péter AU - Tanaka, T AU - Juhász, Gábor AU - Sass, Miklós TI - Rab11 facilitates crosstalk between autophagy and endosomal pathway through regulation of Hook localization. JF - MOLECULAR BIOLOGY OF THE CELL J2 - MOL BIOL CELL VL - 25 PY - 2014 IS - 4 SP - 522 EP - 531 PG - 10 SN - 1059-1524 DO - 10.1091/mbc.E13-10-0574 UR - https://m2.mtmt.hu/api/publication/2483302 ID - 2483302 N1 - Funding Agency and Grant Number: Hungarian Scientific Research FundsOrszagos Tudomanyos Kutatasi Alapprogramok (OTKA) [NK78012]; European UnionEuropean Commission [TAMOP 4.2.1./B-09/KMR-2010-0003]; European Social FundEuropean Social Fund (ESF) [TAMOP 4.2.1./B-09/KMR-2010-0003]; Hungarian Academy of SciencesHungarian Academy of Sciences [F01/031] Funding text: This work was supported by a grant from the Hungarian Scientific Research Funds (NK78012) provided to M.S. The European Union and the European Social Fund have provided financial support to this project under grant agreement no. TAMOP 4.2.1./B-09/KMR-2010-0003. T.F. was supported by the Hungarian Academy of Sciences (F01/031). We address special thanks to Helmut Kramer for the indicated antibodies, stocks, and constructs. We are thankful to Janos Elek for the colocalization analysis script in Matlab software. AB - During autophagy, double-membrane autophagosomes deliver sequestered cytoplasmic content to late endosomes and lysosomes for degradation. The molecular mechanism of autophagosome maturation is still poorly characterized. The small GTPase Rab11 regulates endosomal traffic, and is thought to function at the level of recycling endosomes. Here we show that loss of Rab11 leads to accumulation of autophagosomes and late endosomes in Drosophila melanogaster. Rab11 translocates from recycling endosomes to autophagosomes in response to autophagy induction, and physically interacts with Hook, a negative regulator of endosome maturation. Hook anchors endosomes to microtubules, and we show that Rab11 facilitates the fusion of endosomes and autophagosomes by removing Hook from mature late endosomes and inhibiting its homodimerization. Thus, induction of autophagy appears to promote autophagic flux by increased convergence with the endosomal pathway. LA - English DB - MTMT ER - TY - BOOK AU - Sass, Miklós AU - Lippai, Mónika AU - László, Lajos AU - Pálfa, Zsolt AU - Kovács, János AU - Laskay, Gábor AU - Szigeti, Csaba ED - Sass, Miklós ED - Laskay, Gábor TI - Molekuláris sejtbiológia ET - 0 PB - ELTE Természettudományi Kar CY - Budapest PY - 2013 UR - https://m2.mtmt.hu/api/publication/3061796 ID - 3061796 LA - Hungarian DB - MTMT ER -