@article{MTMT:35639179, title = {Amino Acid and Glucose Fermentation Maintain ATP Content in Mouse and Human Malignant Glioma Cells.}, url = {https://m2.mtmt.hu/api/publication/35639179}, author = {Lee, Derek C and Ta, Linh and Mukherjee, Purna and Duraj, Tomas and Domin, Marek and Greenwood, Bennett and Karmacharya, Srada and Narain, Niven R and Kiebish, Michael and Chinopoulos, Christos and Seyfried, Thomas N}, doi = {10.1080/17590914.2024.2422268}, journal-iso = {ASN NEURO}, journal = {ASN NEURO}, volume = {16}, unique-id = {35639179}, issn = {1759-0914}, abstract = {Energy is necessary for tumor cell viability and growth. Aerobic glucose-driven lactic acid fermentation is a common metabolic phenotype seen in most cancers including malignant gliomas. This metabolic phenotype is linked to abnormalities in mitochondrial structure and function. A luciferin-luciferase bioluminescence ATP assay was used to measure the influence of amino acids, glucose, and oxygen on ATP content and viability in mouse (VM-M3 and CT-2A) and human (U-87MG) glioma cells that differed in cell biology, genetic background, and species origin. Oxygen consumption was measured using the Resipher system. Extracellular lactate and succinate were measured as end products of the glycolysis and glutaminolysis pathways, respectively. The results showed that: (1) glutamine was a source of ATP content irrespective of oxygen. No other amino acid could replace glutamine in sustaining ATP content and viability; (2) ATP content persisted in the absence of glucose and under hypoxia, ruling out substantial contribution through either glycolysis or oxidative phosphorylation (OxPhos) under these conditions; (3) Mitochondrial complex IV inhibition showed that oxygen consumption was not an accurate measure for ATP production through OxPhos. The glutaminase inhibitor, 6-diazo-5-oxo-L-norleucine (DON), reduced ATP content and succinate export in cells grown in glutamine. The data suggests that mitochondrial substrate level phosphorylation in the glutamine-driven glutaminolysis pathway contributes to ATP content in these glioma cells. A new model is presented highlighting the synergistic interaction between the high-throughput glycolysis and glutaminolysis pathways that drive malignant glioma growth and maintain ATP content through the aerobic fermentation of both glucose and glutamine.}, keywords = {FERMENTATION; glioblastoma; SUCCINATE; Glutaminolysis; mitochondrial substrate level phosphorylation}, year = {2024}, eissn = {1759-0914}, orcid-numbers = {Chinopoulos, Christos/0000-0003-0183-4149} } @article{MTMT:35626090, title = {Residual Complex I activity and amphidirectional Complex II operation support glutamate catabolism through mtSLP in anoxia}, url = {https://m2.mtmt.hu/api/publication/35626090}, author = {Ravasz, Dóra and Bui, Dávid and Nazarian, Sara and Pallag, Gergely and Karnok, Noémi and Roberts, Jennie and Marzullo, Bryan P. and Tennant, Daniel A. and Greenwood, Bennett and Kitayev, Alex and Hill, Collin and Komlódi, Tímea and Doerrier, Carolina and Cunatova, Kristyna and Fernandez-Vizarra, Erika and Gnaiger, Erich and Kiebish, Michael A. and Raska, Alexandra and Kolev, Kraszimir Nikolaev and Czumbel, Bence and Narain, Niven R. and Seyfried, Thomas N. and Chinopoulos, Christos}, doi = {10.1016/j.bbadis.2024.167388}, journal-iso = {BBA-MOL BASIS DIS}, journal = {BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR BASIS OF DISEASE}, volume = {1870}, unique-id = {35626090}, issn = {0925-4439}, year = {2024}, eissn = {1879-260X}, pages = {167388}, orcid-numbers = {Ravasz, Dóra/0000-0002-0510-3282; Bui, Dávid/0000-0003-3726-2031; Pallag, Gergely/0000-0003-4093-162X; Karnok, Noémi/0000-0002-1832-368X; Komlódi, Tímea/0000-0001-9876-1411; Raska, Alexandra/0000-0002-5348-2264; Kolev, Kraszimir Nikolaev/0000-0002-5612-004X; Chinopoulos, Christos/0000-0003-0183-4149} } @article{MTMT:35595842, title = {Neutrophil Extracellular Traps: shaping fibrinolysis and fibrin structure in vivo and ex vivo}, url = {https://m2.mtmt.hu/api/publication/35595842}, author = {Raska, Alexandra and Balog Virág, Kata and Csikós, Petra (Metta) and Szabó, László and Kolev, Kraszimir Nikolaev and Wohner, Nikolett}, journal-iso = {Res Pract Thromb Haemost}, journal = {RESEARCH AND PRACTICE IN THROMBOSIS AND HAEMOSTASIS}, volume = {8}, unique-id = {35595842}, year = {2024}, eissn = {2475-0379}, pages = {76-77}, orcid-numbers = {Raska, Alexandra/0000-0002-5348-2264; Balog Virág, Kata/0000-0002-2291-0705; Kolev, Kraszimir Nikolaev/0000-0002-5612-004X} } @article{MTMT:35595783, title = {The role of factor XIII in modulating the efficacy of tranexamic acid on fibrinolysis and fibrin structure in cellular and cell-free environments}, url = {https://m2.mtmt.hu/api/publication/35595783}, author = {Balog Virág, Kata and B., Egri and Szabó, László and Kolev, Kraszimir Nikolaev and Wohner, Nikolett}, journal-iso = {Res Pract Thromb Haemost}, journal = {RESEARCH AND PRACTICE IN THROMBOSIS AND HAEMOSTASIS}, volume = {8}, unique-id = {35595783}, year = {2024}, eissn = {2475-0379}, pages = {73}, orcid-numbers = {Balog Virág, Kata/0000-0002-2291-0705; Kolev, Kraszimir Nikolaev/0000-0002-5612-004X} } @article{MTMT:35594849, title = {A conserved mechanism couples cytosolic domain movements to pore gating in the TRPM2 channel}, url = {https://m2.mtmt.hu/api/publication/35594849}, author = {Tóth, Balázs and Jiang, Yuefeng and Szöllősi, András and Zhang, Zhe and Csanády, László}, doi = {10.1073/pnas.2415548121}, journal-iso = {P NATL ACAD SCI USA}, journal = {PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA}, volume = {121}, unique-id = {35594849}, issn = {0027-8424}, abstract = {Transient Receptor Potential Melastatin 2 (TRPM2) cation channels contribute to immunocyte activation, insulin secretion, and central thermoregulation. TRPM2 opens upon binding cytosolic Ca 2+ and ADP ribose (ADPR). We present here the 2.5 Å cryo-electronmicroscopy structure of TRPM2 from Nematostella vectensis (nvTRPM2) in a lipid nanodisc, complexed with Ca 2+ and ADPR-2′-phosphate. Comparison with nvTRPM2 without nucleotide reveals that nucleotide binding-induced movements in the protein’s three “core” layers deconvolve into a set of rigid-body rotations conserved from cnidarians to man. By covalently crosslinking engineered cysteine pairs we systematically trap the cytosolic layers in specific conformations and study effects on gate opening/closure. The data show that nucleotide binding in Layer 3 disrupts inhibitory intersubunit interactions, allowing rotation of Layer 2 which in turn expands the gate located in Layer 1. Channels trapped in that “activated” state are no longer nucleotide dependent, but are opened by binding of Ca 2+ alone.}, year = {2024}, eissn = {1091-6490}, orcid-numbers = {Tóth, Balázs/0000-0002-1257-2597; Jiang, Yuefeng/0000-0003-3985-2027; Szöllősi, András/0000-0002-5570-4609; Zhang, Zhe/0000-0002-4932-4343; Csanády, László/0000-0002-6547-5889} } @article{MTMT:35573142, title = {Neutrophil extracelluláris csapdák hatása a fibrinolízisre és fibrin szerkezetre in vivo és ex vivo}, url = {https://m2.mtmt.hu/api/publication/35573142}, author = {Raska, Alexandra and Baráth, Barbara and Balog Virág, Kata and Csikós, P and Szabó, László and Kolev, Kraszimir Nikolaev and Wohner, Nikolett}, journal-iso = {HEMATOLÓGIA-TRANSZFUZIOLÓGIA}, journal = {HEMATOLÓGIA-TRANSZFUZIOLÓGIA}, volume = {57}, unique-id = {35573142}, issn = {1786-5913}, year = {2024}, pages = {187-188}, orcid-numbers = {Raska, Alexandra/0000-0002-5348-2264; Balog Virág, Kata/0000-0002-2291-0705; Kolev, Kraszimir Nikolaev/0000-0002-5612-004X} } @article{MTMT:35573125, title = {A natív és citrullinált core-hisztonok kringle-dependens módon gátolják a plazmin fibrin(ogeno)lítikus aktivitását}, url = {https://m2.mtmt.hu/api/publication/35573125}, author = {Komorowicz, Erzsébet and Gurabi, A and Sándor, Z and Wacha, András Ferenc and Kolev, Kraszimir Nikolaev}, doi = {10.1556/2068.2024.30001}, journal-iso = {HEMATOLÓGIA-TRANSZFUZIOLÓGIA}, journal = {HEMATOLÓGIA-TRANSZFUZIOLÓGIA}, volume = {57}, unique-id = {35573125}, issn = {1786-5913}, year = {2024}, pages = {183-184}, orcid-numbers = {Komorowicz, Erzsébet/0000-0002-4860-3498; Wacha, András Ferenc/0000-0002-9609-0893; Kolev, Kraszimir Nikolaev/0000-0002-5612-004X} } @article{MTMT:35573094, title = {A XIII-as faktor szerepe a tranexámsav fibrinolízisre és fibrinszerkezetre kifejtett hatásának modulálásában sejtes és sejtmentes környezetben}, url = {https://m2.mtmt.hu/api/publication/35573094}, author = {Balog Virág, Kata and Egri, B and Szabó, László and Kolev, Kraszimir Nikolaev and Wohner, Nikolett}, journal-iso = {HEMATOLÓGIA-TRANSZFUZIOLÓGIA}, journal = {HEMATOLÓGIA-TRANSZFUZIOLÓGIA}, volume = {57}, unique-id = {35573094}, issn = {1786-5913}, year = {2024}, pages = {172}, orcid-numbers = {Balog Virág, Kata/0000-0002-2291-0705; Kolev, Kraszimir Nikolaev/0000-0002-5612-004X} } @article{MTMT:35501499, title = {Structural determinants of protein kinase A essential for CFTR channel activation.}, url = {https://m2.mtmt.hu/api/publication/35501499}, author = {Mihályi, Csaba and Iordanov, Iordan and Szöllősi, András and Csanády, László}, doi = {10.1073/pnas.2407728121}, journal-iso = {P NATL ACAD SCI USA}, journal = {PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA}, volume = {121}, unique-id = {35501499}, issn = {0027-8424}, abstract = {Cystic Fibrosis Transmembrane Conductance Regulator (CFTR), the anion channel mutated in cystic fibrosis (CF) patients, is activated by the catalytic subunit of protein kinase A (PKA-C). PKA-C activates CFTR both noncatalytically, through binding, and catalytically, through phosphorylation of multiple serines in CFTR's regulatory (R) domain. Here, we identify key molecular determinants of the CFTR/PKA-C interaction essential for these processes. By comparing CFTR current activation in the presence of ATP or an ATP analog unsuitable for phosphotransfer, as well as pseudosubstrate peptides of various lengths, we identify two distinct specific regions of the PKA-C surface which interact with CFTR to cause noncatalytic and catalytic CFTR stimulation, respectively. Whereas the "substrate site" mediates CFTR phosphorylation, a distinct hydrophobic patch (the "docking site") is responsible for noncatalytic CFTR activation, achieved by stabilizing the R domain in a "released" conformation permissive to channel gating. Furthermore, by comparing PKA-C variants with different posttranslational modification patterns, we find that direct membrane tethering of the kinase through its N-terminal myristoyl group is an unappreciated fundamental requirement for CFTR activation: PKA-C demyristoylation abolishes noncatalytic, and profoundly slows catalytic, CFTR stimulation. For the F508del CFTR mutant, present in ~90% of CF patients, maximal activation by demyristoylated PKA-C is reduced by ~10-fold compared to that by myristoylated PKA-C. Finally, in bacterial genera that contain common CF pathogens, we identify virulence factors that demyristoylate PKA-C in vitro, raising the possibility that during recurrent bacterial infections in CF patients, PKA-C demyristoylation may contribute to the exacerbation of lung disease.}, keywords = {cystic fibrosis; cAMP-dependent protein kinase; N-myristoylation; IpaJ; PKI peptide}, year = {2024}, eissn = {1091-6490}, orcid-numbers = {Mihályi, Csaba/0000-0001-7536-3066; Iordanov, Iordan/0000-0001-8251-5857; Szöllősi, András/0000-0002-5570-4609; Csanády, László/0000-0002-6547-5889} } @article{MTMT:35501481, title = {The structures of protein kinase A in complex with CFTR. Mechanisms of phosphorylation and noncatalytic activation.}, url = {https://m2.mtmt.hu/api/publication/35501481}, author = {Fiedorczuk, Karol and Iordanov, Iordan and Mihályi, Csaba and Szöllősi, András and Csanády, László and Chen, Jue}, doi = {10.1073/pnas.2409049121}, journal-iso = {P NATL ACAD SCI USA}, journal = {PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA}, volume = {121}, unique-id = {35501481}, issn = {0027-8424}, abstract = {Protein kinase A (PKA) is a key regulator of cellular functions by selectively phosphorylating numerous substrates, including ion channels, enzymes, and transcription factors. It has long served as a model system for understanding the eukaryotic kinases. Using cryoelectron microscopy, we present complex structures of the PKA catalytic subunit (PKA-C) bound to a full-length protein substrate, the cystic fibrosis transmembrane conductance regulator (CFTR)-an ion channel vital to human health. CFTR gating requires phosphorylation of its regulatory (R) domain. Unphosphorylated CFTR engages PKA-C at two locations, establishing two "catalytic stations" near to, but not directly involving, the R domain. This configuration, coupled with the conformational flexibility of the R domain, permits transient interactions of the eleven spatially separated phosphorylation sites. Furthermore, we determined two structures of the open-pore CFTR stabilized by PKA-C, providing a molecular basis to understand how PKA-C stimulates CFTR currents even in the absence of phosphorylation.}, keywords = {PHOSPHORYLATION; Complex structure; CFTR; protein kinase A; reversible activation}, year = {2024}, eissn = {1091-6490}, orcid-numbers = {Iordanov, Iordan/0000-0001-8251-5857; Mihályi, Csaba/0000-0001-7536-3066; Szöllősi, András/0000-0002-5570-4609; Csanády, László/0000-0002-6547-5889} }