@article{MTMT:34720489,
	title = {Reviewing critical TRPM2 variants through a structure-function lens},
	url = {https://m2.mtmt.hu/api/publication/34720489},
	author = {Tóth, Ádám Viktor and Bartók, Ádám},
	doi = {10.1016/j.jbiotec.2024.02.017},
	journal-iso = {J BIOTECHNOL},
	journal = {JOURNAL OF BIOTECHNOLOGY},
	volume = {385},
	unique-id = {34720489},
	issn = {0168-1656},
	year = {2024},
	eissn = {1873-4863},
	pages = {49-57},
	orcid-numbers = {Bartók, Ádám/0000-0002-1232-5246}
}

@article{MTMT:34507016,
	title = {Towards personalized medicine for cystic fibrosis patients with rare mutations},
	url = {https://m2.mtmt.hu/api/publication/34507016},
	author = {Csanády, László},
	doi = {10.1113/JP286135},
	journal-iso = {J PHYSIOL-LONDON},
	journal = {JOURNAL OF PHYSIOLOGY-LONDON},
	volume = {602},
	unique-id = {34507016},
	issn = {0022-3751},
	keywords = {personalized medicine; cystic fibrosis; Neurosciences},
	year = {2024},
	eissn = {1469-7793},
	pages = {257-258},
	orcid-numbers = {Csanády, László/0000-0002-6547-5889}
}

@article{MTMT:34502176,
	title = {TRPM2 - an adjustable thermostat},
	url = {https://m2.mtmt.hu/api/publication/34502176},
	author = {Bartók, Ádám and Csanády, László},
	doi = {10.1016/j.ceca.2024.102850},
	journal-iso = {CELL CALCIUM},
	journal = {CELL CALCIUM},
	volume = {118},
	unique-id = {34502176},
	issn = {0143-4160},
	year = {2024},
	eissn = {1532-1991},
	orcid-numbers = {Bartók, Ádám/0000-0002-1232-5246; Csanády, László/0000-0002-6547-5889}
}

@article{MTMT:34232792,
	title = {Estimating the true stability of the prehydrolytic outward-facing state in an ABC protein.},
	url = {https://m2.mtmt.hu/api/publication/34232792},
	author = {Simon, Márton and Iordanov, Iordan and Szöllősi, András and Csanády, László},
	doi = {10.7554/eLife.90736},
	journal-iso = {ELIFE},
	journal = {ELIFE},
	volume = {12},
	unique-id = {34232792},
	issn = {2050-084X},
	abstract = {CFTR, the anion channel mutated in cystic fibrosis patients, is a model ABC protein whose ATP-driven conformational cycle is observable at single-molecule level in patch-clamp recordings. Bursts of CFTR pore openings are coupled to tight dimerization of its two nucleotide-binding domains (NBDs) and in wild-type (WT) channels are mostly terminated by ATP hydrolysis. The slow rate of non-hydrolytic closure - which determines how tightly bursts and ATP hydrolysis are coupled - is unknown, as burst durations of catalytic site mutants span a range of ~200-fold. Here, we show that Walker A mutation K1250A, Walker B mutation D1370N, and catalytic glutamate mutations E1371S and E1371Q all completely disrupt ATP hydrolysis. True non-hydrolytic closing rate of WT CFTR approximates that of K1250A and E1371S. That rate is slowed ~15-fold in E1371Q by a non-native inter-NBD H-bond, and accelerated ~15-fold in D1370N. These findings uncover unique features of the NBD interface in human CFTR.},
	keywords = {ZEBRAFISH; Xenopus; molecular biophysics; Structural biology; D-loop; composite ATP-binding site; flickery closure; mutant cycle},
	year = {2023},
	eissn = {2050-084X},
	orcid-numbers = {Iordanov, Iordan/0000-0001-8251-5857; Szöllősi, András/0000-0002-5570-4609; Csanády, László/0000-0002-6547-5889}
}

@article{MTMT:34064647,
	title = {Functional characterization of the transient receptor potential melastatin 2 (TRPM2) cation channel from Nematostella vectensis reconstituted into lipid bilayer},
	url = {https://m2.mtmt.hu/api/publication/34064647},
	author = {Szöllősi, András and Almássy, János},
	doi = {10.1038/s41598-023-38640-6},
	journal-iso = {SCI REP},
	journal = {SCIENTIFIC REPORTS},
	volume = {13},
	unique-id = {34064647},
	issn = {2045-2322},
	abstract = {Transient receptor potential melastatin 2 (TRPM2) cation channel activity is required for insulin secretion, immune cell activation and body heat control. Channel activation upon oxidative stress is involved in the pathology of stroke and neurodegenerative disorders. Cytosolic Ca 2+ , ADP-ribose (ADPR) and phosphatidylinositol-4,5-bisphosphate (PIP 2 ) are the obligate activators of the channel. Several TRPM2 cryo-EM structures have been resolved to date, yet functionality of the purified protein has not been tested. Here we reconstituted overexpressed and purified TRPM2 from Nematostella vectensis (nvTRPM2) into lipid bilayers and found that the protein is fully functional. Consistent with the observations in native membranes, nvTRPM2 in lipid bilayers is co-activated by cytosolic Ca 2+ and either ADPR or ADPR-2′-phosphate (ADPRP). The physiological metabolite ADPRP has a higher apparent affinity than ADPR. In lipid bilayers nvTRPM2 displays a large linear unitary conductance, its open probability (P o ) shows little voltage dependence and is stable over several minutes. P o is high without addition of exogenous PIP 2 , but is largely blunted by treatment with poly- l -Lysine, a polycation that masks PIP 2 headgroups. These results indicate that PIP 2 or some other activating phosphoinositol lipid co-purifies with nvTRPM2, suggesting a high PIP 2 binding affinity of nvTRPM2 under physiological conditions.},
	year = {2023},
	eissn = {2045-2322},
	orcid-numbers = {Szöllősi, András/0000-0002-5570-4609}
}

@article{MTMT:33755807,
	title = {Blue flash sheds light on the roles of individual phosphoserines in CFTR channel activation},
	url = {https://m2.mtmt.hu/api/publication/33755807},
	author = {Csanády, László},
	doi = {10.1085/jgp.202313336},
	journal-iso = {J GEN PHYSIOL},
	journal = {JOURNAL OF GENERAL PHYSIOLOGY},
	volume = {155},
	unique-id = {33755807},
	issn = {0022-1295},
	year = {2023},
	eissn = {1540-7748},
	orcid-numbers = {Csanády, László/0000-0002-6547-5889}
}

@article{MTMT:33666263,
	title = {Investigation of factors that influence the temperature sensitivity of the TRPM2 cation channel},
	url = {https://m2.mtmt.hu/api/publication/33666263},
	author = {Bartók, Ádám},
	doi = {10.1016/j.bpj.2022.11.775},
	journal-iso = {BIOPHYS J},
	journal = {BIOPHYSICAL JOURNAL},
	volume = {122},
	unique-id = {33666263},
	issn = {0006-3495},
	year = {2023},
	eissn = {1542-0086},
	pages = {110a-110a},
	orcid-numbers = {Bartók, Ádám/0000-0002-1232-5246}
}

@article{MTMT:33636409,
	title = {Optimization of CFTR gating through the evolution of its extracellular loops},
	url = {https://m2.mtmt.hu/api/publication/33636409},
	author = {Simon, Márton and Csanády, László},
	doi = {10.1085/jgp.202213264},
	journal-iso = {J GEN PHYSIOL},
	journal = {JOURNAL OF GENERAL PHYSIOLOGY},
	volume = {155},
	unique-id = {33636409},
	issn = {0022-1295},
	year = {2023},
	eissn = {1540-7748},
	orcid-numbers = {Csanády, László/0000-0002-6547-5889}
}

@article{MTMT:33262968,
	title = {Dual amplification strategy turns TRPM2 channels into supersensitive central heat detectors},
	url = {https://m2.mtmt.hu/api/publication/33262968},
	author = {Bartók, Ádám and Csanády, László},
	doi = {10.1073/pnas.2212378119},
	journal-iso = {P NATL ACAD SCI USA},
	journal = {PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA},
	volume = {119},
	unique-id = {33262968},
	issn = {0027-8424},
	abstract = {The Ca 2+ and ADP ribose (ADPR)-activated cation channel TRPM2 is the closest homolog of the cold sensor TRPM8 but serves as a deep-brain warmth sensor. To unravel the molecular mechanism of heat sensing by the TRPM2 protein, we study here temperature dependence of TRPM2 currents in cell-free membrane patches across ranges of agonist concentrations. We find that channel gating remains strictly agonist-dependent even at 40°C: heating alone or in combination with just Ca 2+ , just ADPR, Ca 2+ + cyclic ADPR, or H 2 O 2 pretreatment only marginally activates TRPM2. For fully liganded TRPM2, pore opening is intrinsically endothermic, due to ~10-fold larger activation enthalpy for opening (~200 kJ/mol) than for closure (~20 kJ/mol). However, the temperature threshold is too high (>40°C) for unliganded but too low (<15°C) for fully liganded channels. Thus, warmth sensitivity around 37°C is restricted to narrow ranges of agonist concentrations. For ADPR, that range matches, but for Ca 2+ , it exceeds bulk cytosolic values. The supraphysiological [Ca 2+ ] needed for TRPM2 warmth sensitivity is provided by Ca 2+ entering through the channel’s pore. That positive feedback provides further strong amplification to the TRPM2 temperature response (Q 10 ~ 1,000), enabling the TRPM2 protein to autonomously respond to tiny temperature fluctuations around 37°C. These functional data together with published structures suggest a molecular mechanism for opposite temperature dependences of two closely related channel proteins.},
	year = {2022},
	eissn = {1091-6490},
	orcid-numbers = {Bartók, Ádám/0000-0002-1232-5246; Csanády, László/0000-0002-6547-5889}
}

@article{MTMT:33070137,
	title = {Reverse and Forward Electron Flow-Induced H2O2 Formation Is Decreased in α-Ketoglutarate Dehydrogenase (α-KGDH) Subunit (E2 or E3) Heterozygote Knock Out Animals},
	url = {https://m2.mtmt.hu/api/publication/33070137},
	author = {Horváth, Gergő and Sváb, Gergely and Komlódi, Tímea and Ravasz, Dóra and Kacsó, Gergely and Dóczi, Judit and Chinopoulos, Christos and Ambrus, Attila and Tretter, László},
	doi = {10.3390/antiox11081487},
	journal-iso = {ANTIOXIDANTS-BASEL},
	journal = {ANTIOXIDANTS},
	volume = {11},
	unique-id = {33070137},
	abstract = {α-ketoglutarate dehydrogenase complex (KGDHc), or 2-oxoglutarate dehydrogenase complex (OGDHc) is a rate-limiting enzyme in the tricarboxylic acid cycle, that has been identified in neurodegenerative diseases such as in Alzheimer’s disease. The aim of the present study was to establish the role of the KGDHc and its subunits in the bioenergetics and reactive oxygen species (ROS) homeostasis of brain mitochondria. To study the bioenergetic profile of KGDHc, genetically modified mouse strains were used having a heterozygous knock out (KO) either in the dihydrolipoyl succinyltransferase (DLST+/−) or in the dihydrolipoyl dehydrogenase (DLD+/−) subunit. Mitochondrial oxygen consumption, hydrogen peroxide (H2O2) production, and expression of antioxidant enzymes were measured in isolated mouse brain mitochondria. Here, we demonstrate that the ADP-stimulated respiration of mitochondria was partially arrested in the transgenic animals when utilizing α-ketoglutarate (α-KG or 2-OG) as a fuel substrate. Succinate and α-glycerophosphate (α-GP), however, did not show this effect. The H2O2 production in mitochondria energized with α-KG was decreased after inhibiting the adenine nucleotide translocase and Complex I (CI) in the transgenic strains compared to the controls. Similarly, the reverse electron transfer (RET)-evoked H2O2 formation supported by succinate or α-GP were inhibited in mitochondria isolated from the transgenic animals. The decrease of RET-evoked ROS production by DLST+/− or DLD+/− KO-s puts the emphasis of the KGDHc in the pathomechanism of ischemia-reperfusion evoked oxidative stress. Supporting this notion, expression of the antioxidant enzyme glutathione peroxidase was also decreased in the KGDHc transgenic animals suggesting the attenuation of ROS-producing characteristics of KGDHc. These findings confirm the contribution of the KGDHc to the mitochondrial ROS production and in the pathomechanism of ischemia-reperfusion injury.},
	year = {2022},
	eissn = {2076-3921},
	orcid-numbers = {Horváth, Gergő/0000-0001-5386-9509; Sváb, Gergely/0000-0002-7669-8252; Komlódi, Tímea/0000-0001-9876-1411; Ravasz, Dóra/0000-0002-0510-3282; Kacsó, Gergely/0000-0003-0428-3645; Dóczi, Judit/0000-0002-5797-5074; Chinopoulos, Christos/0000-0003-0183-4149; Ambrus, Attila/0000-0001-6014-3175; Tretter, László/0000-0001-5638-2886}
}