@article{MTMT:34770405, title = {International consensus guidelines for the definition, detection, and interpretation of autophagy-dependent ferroptosis}, url = {https://m2.mtmt.hu/api/publication/34770405}, author = {Chen, Xin and Tsvetkov, Andrey S. and Shen, Han-Ming and Isidoro, Ciro and Ktistakis, Nicholas T. and Linkermann, Andreas and Koopman, Werner J. H. and Simon, Hans-Uwe and Galluzzi, Lorenzo and Luo, Shouqing and Xu, Daqian and Gu, Wei and Peulen, Olivier and Cai, Qian and Rubinsztein, David C. and Chi, Jen-Tsan and Zhang, Donna D. and Li, Changfeng and Toyokuni, Shinya and Liu, Jinbao and Roh, Jong-Lyel and Dai, Enyong and Juhász, Gábor and Liu, Wei and Zhang, Jianhua and Yang, Minghua and Liu, Jiao and Zhu, Ling-Qiang and Zou, Weiping and Piacentini, Mauro and Ding, Wen-Xing and Yue, Zhenyu and Xie, Yangchun and Petersen, Morten and Gewirtz, David A. and Mandell, Michael A. and Chu, Charleen T. and Sinha, Debasish and Eftekharpour, Eftekhar and Zhivotovsky, Boris and Besteiro, Sebastien and Gabrilovich, Dmitry I. and Kim, Do-Hyung and Kagan, Valerian E. and Bayir, Hulya and Chen, Guang-Chao and Ayton, Scott and Luenemann, Jan D. and Komatsu, Masaaki and Krautwald, Stefan and Loos, Ben and Baehrecke, Eric H. and Wang, Jiayi and Lane, Jon D. and Sadoshima, Junichi and Yang, Wan Seok and Gao, Minghui and Munz, Christian and Thumm, Michael and Kampmann, Martin and Yu, Di and Lipinski, Marta M. and Jones, Jace W. and Jiang, Xuejun and Zeh, Herbert J. and Kang, Rui and Klionsky, Daniel J. and Kroemer, Guido and Tang, Daolin}, doi = {10.1080/15548627.2024.2319901}, journal-iso = {AUTOPHAGY}, journal = {AUTOPHAGY}, unique-id = {34770405}, issn = {1554-8627}, abstract = {Macroautophagy/autophagy is a complex degradation process with a dual role in cell death that is influenced by the cell types that are involved and the stressors they are exposed to. Ferroptosis is an iron-dependent oxidative form of cell death characterized by unrestricted lipid peroxidation in the context of heterogeneous and plastic mechanisms. Recent studies have shed light on the involvement of specific types of autophagy (e.g. ferritinophagy, lipophagy, and clockophagy) in initiating or executing ferroptotic cell death through the selective degradation of anti-injury proteins or organelles. Conversely, other forms of selective autophagy (e.g. reticulophagy and lysophagy) enhance the cellular defense against ferroptotic damage. Dysregulated autophagy-dependent ferroptosis has implications for a diverse range of pathological conditions. This review aims to present an updated definition of autophagy-dependent ferroptosis, discuss influential substrates and receptors, outline experimental methods, and propose guidelines for interpreting the results.Abbreviation: 3-MA:3-methyladenine; 4HNE: 4-hydroxynonenal; ACD: accidentalcell death; ADF: autophagy-dependentferroptosis; ARE: antioxidant response element; BH2:dihydrobiopterin; BH4: tetrahydrobiopterin; BMDMs: bonemarrow-derived macrophages; CMA: chaperone-mediated autophagy; CQ:chloroquine; DAMPs: danger/damage-associated molecular patterns; EMT,epithelial-mesenchymal transition; EPR: electronparamagnetic resonance; ER, endoplasmic reticulum; FRET: Forsterresonance energy transfer; GFP: green fluorescent protein;GSH: glutathione;IF: immunofluorescence; IHC: immunohistochemistry; IOP, intraocularpressure; IRI: ischemia-reperfusion injury; LAA: linoleamide alkyne;MDA: malondialdehyde; PGSK: Phen Green (TM) SK;RCD: regulatedcell death; PUFAs: polyunsaturated fatty acids; RFP: red fluorescentprotein;ROS: reactive oxygen species; TBA: thiobarbituricacid; TBARS: thiobarbituric acid reactive substances; TEM:transmission electron microscopy.}, keywords = {LIPID-PEROXIDATION; MASS-SPECTROMETRY; PROTEIN; CANCER-CELLS; Lipid Peroxidation; IRON; Cell Death; acute kidney injury; transcription factor Nrf2; Lipophagy; ferritinophagy; ferritinophagy; ERASTIN-INDUCED FERROPTOSIS; NONAPOPTOTIC CELL-DEATH}, year = {2024}, eissn = {1554-8635}, orcid-numbers = {Simon, Hans-Uwe/0000-0002-9404-7736; Juhász, Gábor/0000-0001-8548-8874; Ayton, Scott/0000-0002-3479-2427; Lane, Jon D./0000-0002-6828-5888} } @article{MTMT:34743202, title = {A bipartite NLS motif mediates the nuclear import of Drosophila moesin}, url = {https://m2.mtmt.hu/api/publication/34743202}, author = {Kovács, Zoltán and Bajusz, Csaba and Szabó, Anikó and Borkúti, Péter and Vedelek, Balázs and Benke, Reka and Lipinszki, Zoltán and Kristó, Ildikó and Vilmos, Péter}, doi = {10.3389/fcell.2024.1206067}, journal-iso = {FRONT CELL DEV BIOL}, journal = {FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY}, volume = {12}, unique-id = {34743202}, issn = {2296-634X}, abstract = {The ERM protein family, which consists of three closely related proteins in vertebrates, ezrin, radixin, and moesin (ERM), is an ancient and important group of cytoplasmic actin-binding and organizing proteins. With their FERM domain, ERMs bind various transmembrane proteins and anchor them to the actin cortex through their C-terminal F-actin binding domain, thus they are major regulators of actin dynamics in the cell. ERMs participate in many fundamental cellular processes, such as phagocytosis, microvilli formation, T-cell activation and tumor metastasis. We have previously shown that, besides its cytoplasmic activities, the single ERM protein of Drosophila melanogaster, moesin, is also present in the cell nucleus, where it participates in gene expression and mRNA export. Here we study the mechanism by which moesin enters the nucleus. We show that the nuclear import of moesin is an NLS-mediated, active process. The nuclear localization sequence of the moesin protein is an evolutionarily highly conserved, conventional bipartite motif located on the surface of the FERM domain. Our experiments also reveal that the nuclear import of moesin does not require PIP2 binding or protein activation, and occurs in monomeric form. We propose, that the balance between the phosphorylated and non-phosphorylated protein pools determines the degree of nuclear import of moesin.}, keywords = {PHOSPHORYLATION; BINDING; LOCALIZATION; IDENTIFICATION; NUCLEUS; STRUCTURAL BASIS; DROSOPHILA; CELL BIOLOGY; ERM PROTEINS; ezrin; moesin; CYTOPLASMIC TAIL; ERM; PIP2; importin; MERLIN; LINKS ACTIN}, year = {2024}, eissn = {2296-634X}, orcid-numbers = {Vedelek, Balázs/0000-0001-6981-0026; Lipinszki, Zoltán/0000-0002-2067-0832} } @article{MTMT:34724664, title = {PtdIns4p is required for the autophagosomal recruitment of STX17 (syntaxin 17) to promote lysosomal fusion}, url = {https://m2.mtmt.hu/api/publication/34724664}, author = {Laczkó-Dobos, Hajnalka and Bhattacharjee, Arindam and Maddali, Asha Kiran and Kincses, András and Abuammar, Hussein and Sebőkné Nagy, Krisztina and Páli, Tibor and Dér, András and Hegedűs, Tamás and Csordás, Gábor and Juhász, Gábor}, doi = {10.1080/15548627.2024.2322493}, journal-iso = {AUTOPHAGY}, journal = {AUTOPHAGY}, volume = {AiP}, unique-id = {34724664}, issn = {1554-8627}, year = {2024}, eissn = {1554-8635}, orcid-numbers = {Páli, Tibor/0000-0003-1649-1097; Hegedűs, Tamás/0000-0002-0331-9629; Csordás, Gábor/0000-0001-6871-6839; Juhász, Gábor/0000-0001-8548-8874} } @{MTMT:34723493, title = {Mikovírusok azonosítása Rhizopus fajokban}, url = {https://m2.mtmt.hu/api/publication/34723493}, author = {Sávai, Gergő and Kartali, Tünde and Benci, Dániel Attila and Patai, Roland and Lipinszki, Zoltán and Vágvölgyi, Csaba and Papp, Tamás}, booktitle = {Biotechnológiai Szakmai Nap Absztraktfüzet}, unique-id = {34723493}, year = {2024}, orcid-numbers = {Lipinszki, Zoltán/0000-0002-2067-0832; Vágvölgyi, Csaba/0000-0003-0009-7773; Papp, Tamás/0000-0001-8211-5431} } @article{MTMT:34575640, title = {Expression and purification of the receptor-binding domain of SARS-CoV-2 spike protein in mammalian cells for immunological assays}, url = {https://m2.mtmt.hu/api/publication/34575640}, author = {Ábrahám, Edit and Bajusz, Csaba and Marton, Annamária and Borics, Attila and Mdluli, Thandiswa and Pardi, Norbert and Lipinszki, Zoltán}, doi = {10.1002/2211-5463.13754}, journal-iso = {FEBS OPEN BIO}, journal = {FEBS OPEN BIO}, volume = {14}, unique-id = {34575640}, issn = {2211-5463}, abstract = {The receptor-binding domain (RBD) of the spike glycoprotein of SARS-CoV-2 virus mediates the interaction with the host cell and is required for virus internalization. It is, therefore, the primary target of neutralizing antibodies. The receptor-binding domain soon became the major target for COVID-19 research and the development of diagnostic tools and new-generation vaccines. Here, we provide a detailed protocol for high-yield expression and one-step affinity purification of recombinant RBD from transiently transfected Expi293F cells. Expi293F mammalian cells can be grown to extremely high densities in a specially formulated serum-free medium in suspension cultures, which makes them an excellent tool for secreted protein production. The highly purified RBD is glycosylated, structurally intact, and forms homomeric complexes. With this quick and easy method, we are able to produce large quantities of RBD (80 mg center dot L-1 culture) that we have successfully used in immunological assays to examine antibody titers and seroconversion after mRNA-based vaccination of mice.}, keywords = {ELISA; protein purification; recombinant rbd; Expi293F mammalian cells; mRNA-LNP vaccination}, year = {2024}, eissn = {2211-5463}, pages = {380-389}, orcid-numbers = {Lipinszki, Zoltán/0000-0002-2067-0832} } @article{MTMT:34575638, title = {FERM domain-containing proteins are active components of the cell nucleus}, url = {https://m2.mtmt.hu/api/publication/34575638}, author = {Borkúti, Péter and Kristó, Ildikó and Szabó, Anikó and Kovács, Zoltán and Vilmos, Péter}, doi = {10.26508/lsa.202302489}, journal-iso = {LIFE SCI ALLIANCE}, journal = {LIFE SCIENCE ALLIANCE}, volume = {7}, unique-id = {34575638}, abstract = {The FERM domain is a conserved and widespread protein module that appeared in the common ancestor of amoebae, fungi, and animals, and is therefore now found in a wide variety of species. The primary function of the FERM domain is localizing to the plasma membrane through binding lipids and proteins of the membrane; thus, for a long time, FERM domain-containing proteins (FDCPs) were considered exclusively cytoskeletal. Although their role in the cytoplasm has been extensively studied, the recent discovery of the presence and importance of cytoskeletal proteins in the nucleus suggests that FDCPs might also play an important role in nuclear function. In this review, we collected data on their nuclear localization, transport, and possible functions, which are still scattered throughout the literature, with special regard to the role of the FERM domain in these processes. With this, we would like to draw attention to the exciting, new dimension of the role of FDCPs, their nuclear activity, which could be an interesting novel direction for future research.}, keywords = {GENE-EXPRESSION; STRUCTURAL BASIS; FOCAL ADHESION; TERMINAL DOMAIN; SUBCELLULAR-LOCALIZATION; Export signal; Ankyrin Repeat; FAK INTERACTION; KINDLIN FAMILY}, year = {2024}, eissn = {2575-1077} } @article{MTMT:34575637, title = {Direct interaction of Su(var)2-10 via the SIM-binding site of the Piwi protein is required for transposon silencing in Drosophila melanogaster}, url = {https://m2.mtmt.hu/api/publication/34575637}, author = {Bence, Melinda and Jankovics, Ferenc and Kristó, Ildikó and Gyetvai, Akos and Vértessy, Beáta (Grolmuszné) and Erdélyi, Miklós}, doi = {10.1111/febs.17073}, journal-iso = {FEBS J}, journal = {FEBS JOURNAL}, unique-id = {34575637}, issn = {1742-464X}, abstract = {Nuclear Piwi/Piwi-interacting RNA complexes mediate co-transcriptional silencing of transposable elements by inducing local heterochromatin formation. In Drosophila, sumoylation plays an essential role in the assembly of the silencing complex; however, the molecular mechanism by which the sumoylation machinery is recruited to the transposon loci is poorly understood. Here, we show that the Drosophila E3 SUMO-ligase Su(var)2-10 directly binds to the Piwi protein. This interaction is mediated by the SUMO-interacting motif-like (SIM-like) structure in the C-terminal domain of Su(var)2-10. We demonstrated that the SIM-like structure binds to a special region found in the MID domain of the Piwi protein, the structure of which is highly similar to the SIM-binding pocket of SUMO proteins. Abrogation of the Su(var)2-10-binding surface of the Piwi protein resulted in transposon derepression in the ovary of adult flies. Based on our results, we propose a model in which the Piwi protein initiates local sumoylation in the silencing complex by recruiting Su(var)2-10 to the transposon loci.}, keywords = {SUBSTRATE; Drosophila melanogaster; Defense; MOTIF; Sumoylation; Sumoylation; SUMO; piRNA pathway; Su(var)2-10; PIWI/piRNA; ENFORCES}, year = {2024}, eissn = {1742-4658} } @article{MTMT:34566006, title = {The Ykt6–Snap29–Syx13 SNARE complex promotes crinophagy via secretory granule fusion with Lamp1 carrier vesicles}, url = {https://m2.mtmt.hu/api/publication/34566006}, author = {Szenci, Győző and Glatz, Gábor and Takáts, Szabolcs and Juhász, Gábor}, doi = {10.1038/s41598-024-53607-x}, journal-iso = {SCI REP}, journal = {SCIENTIFIC REPORTS}, volume = {14}, unique-id = {34566006}, issn = {2045-2322}, abstract = {In the Drosophila larval salivary gland, developmentally programmed fusions between lysosomes and secretory granules (SGs) and their subsequent acidification promote the maturation of SGs that are secreted shortly before puparium formation. Subsequently, ongoing fusions between non-secreted SGs and lysosomes give rise to degradative crinosomes, where the superfluous secretory material is degraded. Lysosomal fusions control both the quality and quantity of SGs, however, its molecular mechanism is incompletely characterized. Here we identify the R-SNARE Ykt6 as a novel regulator of crinosome formation, but not the acidification of maturing SGs. We show that Ykt6 localizes to Lamp1+ carrier vesicles, and forms a SNARE complex with Syntaxin 13 and Snap29 to mediate fusion with SGs. These Lamp1 carriers represent a distinct vesicle population that are functionally different from canonical Arl8+, Cathepsin L+ lysosomes, which also fuse with maturing SGs but are controlled by another SNARE complex composed of Syntaxin 13, Snap29 and Vamp7. Ykt6- and Vamp7-mediated vesicle fusions also determine the fate of SGs, as loss of either of these SNAREs prevents crinosomes from acquiring endosomal PI3P. Our results highlight that fusion events between SGs and different lysosome-related vesicle populations are critical for fine regulation of the maturation and crinophagic degradation of SGs.}, year = {2024}, eissn = {2045-2322}, orcid-numbers = {Szenci, Győző/0000-0003-0359-6869; Takáts, Szabolcs/0000-0003-2139-7740; Juhász, Gábor/0000-0001-8548-8874} } @article{MTMT:34557517, title = {The recruitment of ACF1 and SMARCA5 to DNA lesions relies on ADP-ribosylation dependent chromatin unfolding}, url = {https://m2.mtmt.hu/api/publication/34557517}, author = {Pinto, Eva and Smith, Rebecca and Bigot, Nicolas and Chapuis, Catherine and Timinszky, Gyula and Huet, Sébastien}, doi = {10.1091/mbc.E23-07-0281}, journal-iso = {MOL BIOL CELL}, journal = {MOLECULAR BIOLOGY OF THE CELL}, volume = {35}, unique-id = {34557517}, issn = {1059-1524}, abstract = {ADP-ribosylation signaling orchestrates the recruitment of various repair actors and chromatin remodeling processes promoting access to lesions during the early stages of the DNA damage response. The chromatin remodeler complex ACF, composed of the ATPase subunit SMARCA5/SNF2H and the cofactor ACF1/BAZ1A, is among the factors that accumulate at DNA lesions in an ADP-ribosylation dependent manner. In this work, we show that each subunit of the ACF complex accumulates to DNA breaks independently from its partner. Furthermore, we demonstrate that the recruitment of SMARCA5 and ACF1 to sites of damage is not due to direct binding to the ADP-ribose moieties but due to facilitated DNA binding at relaxed ADP-ribosylated chromatin. Therefore, our work provides new insights regarding the mechanisms underlying the timely accumulation of ACF1 and SMARCA5 to DNA lesions, where they contribute to efficient DNA damage resolution.}, year = {2024}, eissn = {1939-4586} } @article{MTMT:34547380, title = {For the Better or for the Worse? The Effect of Manganese on the Activity of Eukaryotic DNA Polymerases}, url = {https://m2.mtmt.hu/api/publication/34547380}, author = {Bálint, Éva and Unk, Ildikó}, doi = {10.3390/ijms25010363}, journal-iso = {INT J MOL SCI}, journal = {INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES}, volume = {25}, unique-id = {34547380}, issn = {1661-6596}, abstract = {DNA polymerases constitute a versatile group of enzymes that not only perform the essential task of genome duplication but also participate in various genome maintenance pathways, such as base and nucleotide excision repair, non-homologous end-joining, homologous recombination, and translesion synthesis. Polymerases catalyze DNA synthesis via the stepwise addition of deoxynucleoside monophosphates to the 3 ' primer end in a partially double-stranded DNA. They require divalent metal cations coordinated by active site residues of the polymerase. Mg2+ is considered the likely physiological activator because of its high cellular concentration and ability to activate DNA polymerases universally. Mn2+ can also activate the known DNA polymerases, but in most cases, it causes a significant decrease in fidelity and/or processivity. Hence, Mn2+ has been considered mutagenic and irrelevant during normal cellular function. Intriguingly, a growing body of evidence indicates that Mn2+ can positively influence some DNA polymerases by conferring translesion synthesis activity or altering the substrate specificity. Here, we review the relevant literature focusing on the impact of Mn2+ on the biochemical activity of a selected set of polymerases, namely, Pol beta, Pol lambda, and Pol mu, of the X family, as well as Pol iota and Pol eta of the Y family of polymerases, where congruous data implicate the physiological relevance of Mn2+ in the cellular function of these enzymes.}, keywords = {IN-VITRO; CATALYTIC ACTIVITY; STRUCTURAL BASIS; Manganese; KINETIC-ANALYSIS; Nucleotide incorporation; TRANSLESION SYNTHESIS; TRANSLESION SYNTHESIS; RIBONUCLEOTIDE INCORPORATION; Biochemistry & Molecular Biology; DNA polymerases; ERROR-FREE REPLICATION; THYMINE-THYMINE DIMER; INCORPORATION OPPOSITE}, year = {2024}, eissn = {1422-0067} }