@article{MTMT:34583668,
	title = {A non-carboxylative route for the efficient synthesis of central metabolite malonyl-CoA and its derived products},
	url = {https://m2.mtmt.hu/api/publication/34583668},
	author = {Li, Jian and Mu, Xin and Dong, Wenyue and Chen, Yun and Kang, Qianjin and Zhao, Guang and Hou, Jin and Gonzalez, Ramon and Bai, Linquan and Feng, Yan and Yang, Chen and Liu, Tiangang and Tan, Zaigao},
	doi = {10.1038/s41929-023-01103-2},
	journal-iso = {NAT CATAL},
	journal = {NATURE CATALYSIS},
	unique-id = {34583668},
	issn = {2520-1158},
	abstract = {Acetyl coenzyme A (CoA) carboxylation is the natural route for endogenous malonyl-CoA formation; however, this pathway presents slow kinetics, carbon and energy inefficiencies, tight regulations and a complicated architecture. These shortcomings limit flux towards malonyl-CoA and become a bottleneck towards the biosynthesis of malonyl-CoA-derived products (MDPs). Here, we design the non-carboxylative malonyl-CoA pathway as a non-natural route for malonyl-CoA biosynthesis, independent from acetyl-CoA. The designed pathway features enzymes such as beta-alanine-pyruvate transaminase and malonyl-CoA reductase, exhibits fast kinetics and circumvents tight regulations and the architecture associated with the natural pathway. Furthermore, introducing this pathway into microbes enhances the production of MDPs, including short-chain fatty acids and representative phenol, quinone, alkene, aminoglycoside and macrolide polyketide families, such as spinosad. In summary, this malonyl-CoA formation pathway avoids intrinsic inefficiencies of the natural pathway and can serve as a versatile platform for obtaining MDPs that could be used as fuels, fine chemicals and pharmaceuticals.Acetyl-CoA carboxylation is the canonical route for endogenous malonyl-CoA formation in cells. Here, the authors design a non-carboxylative malonyl-CoA pathway independent of acetyl-CoA into multiple microbes for efficient malonyl-CoA-derived natural products biosynthesis.},
	year = {2024},
	eissn = {2520-1158}
}

@article{MTMT:32894110,
	title = {Bypassing the nuclear gate: A non-canonical entry pathway for the mitochondrial pyruvate dehydrogenase complex},
	url = {https://m2.mtmt.hu/api/publication/32894110},
	author = {Boyle, E. and Wilfling, F.},
	doi = {10.1016/j.molcel.2022.02.014},
	journal-iso = {MOL CELL},
	journal = {MOLECULAR CELL},
	volume = {82},
	unique-id = {32894110},
	issn = {1097-2765},
	abstract = {Zervopoulos et al. (2022) propose a non-canonical nuclear import pathway for the functional mitochondrial pyruvate dehydrogenase complex (PDC), facilitated by dynamic MFN2-mediated tethering of mitochondria to the nuclear envelope upon exposure to proliferative stimuli. © 2022 Elsevier Inc.},
	keywords = {metabolism; GENETICS; MICROSCOPY; human; protein localization; Cell Nucleus; Cell Nucleus; Mitochondria; Mitosis; note; mitochondrion; cell nucleus membrane; mitochondrial enzyme; nucleocytoplasmic transport; Nuclear import; Pyruvate Dehydrogenase Complex; Pyruvate Dehydrogenase Complex; Pyruvate Dehydrogenase Complex; nuclear pore complex; mitofusin 2},
	year = {2022},
	eissn = {1097-4164},
	pages = {886-888}
}

@article{MTMT:32894109,
	title = {MFN2-driven mitochondria-to-nucleus tethering allows a non-canonical nuclear entry pathway of the mitochondrial pyruvate dehydrogenase complex},
	url = {https://m2.mtmt.hu/api/publication/32894109},
	author = {Zervopoulos, S.D. and Boukouris, A.E. and Saleme, B. and Haromy, A. and Tejay, S. and Sutendra, G. and Michelakis, E.D.},
	doi = {10.1016/j.molcel.2022.02.003},
	journal-iso = {MOL CELL},
	journal = {MOLECULAR CELL},
	volume = {82},
	unique-id = {32894109},
	issn = {1097-2765},
	abstract = {The mitochondrial pyruvate dehydrogenase complex (PDC) translocates into the nucleus, facilitating histone acetylation by producing acetyl-CoA. We describe a noncanonical pathway for nuclear PDC (nPDC) import that does not involve nuclear pore complexes (NPCs). Mitochondria cluster around the nucleus in response to proliferative stimuli and tether onto the nuclear envelope (NE) via mitofusin-2 (MFN2)-enriched contact points. A decrease in nuclear MFN2 levels decreases mitochondria tethering and nPDC levels. Mitochondrial PDC crosses the NE and interacts with lamin A, forming a ring below the NE before crossing through the lamin layer into the nucleoplasm, in areas away from NPCs. Effective blockage of NPC trafficking does not decrease nPDC levels. The PDC-lamin interaction is maintained during cell division, when lamin depolymerizes and disassembles before reforming daughter nuclear envelopes, providing another pathway for nPDC entry during mitosis. Our work provides a different angle to understanding mitochondria-to-nucleus communication and nuclear metabolism. © 2022 Elsevier Inc.},
	keywords = {Male; metabolism; metabolism; GENETICS; NUCLEUS; LYSINE; ARTICLE; signal transduction; human; immunoblotting; controlled study; Cell Nucleus; Cell Nucleus; Mitochondria; Mitochondria; transmission electron microscopy; Cell Cycle; Acetylation; embryo; human cell; mitochondrion; mitochondrion; protein protein interaction; cell nucleus membrane; cell nucleus membrane; Limit of detection; Acetyl Coenzyme A; Acetyl Coenzyme A; protein trafficking; confocal laser scanning microscopy; Histone acetylation; protein isolation; HISTONE H3; nuclear envelope; Pyruvate Dehydrogenase Complex; Pyruvate Dehydrogenase Complex; Pyruvate Dehydrogenase Complex; Pyruvate Dehydrogenase Complex; lamin C; lamin A; Mitofusin; mitofusin 2; Lamins; Lamin; Lamin; Invagination; Tethering; HFF-1 cell line},
	year = {2022},
	eissn = {1097-4164},
	pages = {1066-1077.e7}
}

@article{MTMT:31836491,
	title = {The plasticity of the pyruvate dehydrogenase complex confers a labile structure that is associated with its catalytic activity},
	url = {https://m2.mtmt.hu/api/publication/31836491},
	author = {Lee, J. and Oh, S. and Bhattacharya, S. and Zhang, Y. and Florens, L. and Washburn, M.P. and Workman, J.L.},
	doi = {10.1371/journal.pone.0243489},
	journal-iso = {PLOS ONE},
	journal = {PLOS ONE},
	volume = {15},
	unique-id = {31836491},
	issn = {1932-6203},
	abstract = {The pyruvate dehydrogenase complex (PDC) is a multienzyme complex that plays a key role in energy metabolism by converting pyruvate to acetyl-CoA. An increase of nuclear PDC has been shown to be correlated with an increase of histone acetylation that requires acetyl-CoA. PDC has been reported to form a ∼ 10 MDa macromolecular machine that is proficient in performing sequential catalytic reactions via its three components. In this study, we show that the PDC displays size versatility in an ionic strength-dependent manner using size exclusion chromatography of yeast cell extracts. Biochemical analysis in combination with mass spectrometry indicates that yeast PDC (yPDC) is a salt-labile complex that dissociates into sub-megadalton individual components even under physiological ionic strength. Interestingly, we find that each oligomeric component of yPDC displays a larger size than previously believed. In addition, we show that the mammalian PDC also displays this uncommon characteristic of salt-lability, although it has a somewhat different profile compared to yeast. We show that the activity of yPDC is reduced in higher ionic strength. Our results indicate that the structure of PDC may not always maintain its ∼ 10 MDa organization, but is rather variable. We propose that the flexible nature of PDC may allow modulation of its activity. © 2020 Lee et al.},
	keywords = {ARTICLE; polymerase chain reaction; immunoblotting; Saccharomyces cerevisiae; controlled study; nonhuman; in vitro study; Mass spectrometry; PROTEIN FUNCTION; Cell Fractionation; proteomics; enzyme structure; incubation time; colorimetry; fungal strain; fungus growth; ionic strength; Histone acetylation; Size exclusion chromatography; Pyruvate Dehydrogenase Complex},
	year = {2021},
	eissn = {1932-6203}
}

@article{MTMT:31936105,
	title = {Structural and functional impact of clinically relevant E1α variants causing pyruvate dehydrogenase complex deficiency},
	url = {https://m2.mtmt.hu/api/publication/31936105},
	author = {Pavlu-Pereira, H. and Lousa, D. and Tomé, C.S. and Florindo, C. and Silva, M.J. and de, Almeida I.T. and Leandro, P. and Rivera, I. and Vicente, J.B.},
	doi = {10.1016/j.biochi.2021.02.007},
	journal-iso = {BIOCHIMIE},
	journal = {BIOCHIMIE},
	volume = {183},
	unique-id = {31936105},
	issn = {0300-9084},
	abstract = {Pyruvate dehydrogenase complex (PDC) catalyzes the oxidative decarboxylation of pyruvate to acetyl-coenzyme A, hinging glycolysis and the tricarboxylic acid cycle. PDC deficiency, an inborn error of metabolism, has a broad phenotypic spectrum. Symptoms range from fatal lactic acidosis or progressive neuromuscular impairment in the neonatal period, to chronic neurodegeneration. Most disease-causing mutations in PDC deficiency affect the PDHA1 gene, encoding the α subunit of the PDC-E1 component. Detailed biophysical analysis of pathogenic protein variants is a challenging approach to support the design of therapies based on improving and correcting protein structure and function. Herein, we report the characterization of clinically relevant PDC-E1α variants identified in Portuguese PDC deficient patients. These variants bear amino acid substitutions in different structural regions of PDC-E1α. The structural and functional analyses of recombinant heterotetrameric (αα’ββ’) PDC-E1 variants, combined with molecular dynamics (MD) simulations, show a limited impact of the amino acid changes on the conformational stability, apart from the increased propensity for aggregation of the p.R253G variant as compared to wild-type PDC-E1. However, all variants presented a functional impairment in terms of lower residual PDC-E1 enzymatic activity and ≈3–100 × lower affinity for the thiamine pyrophosphate (TPP) cofactor, in comparison with wild-type PDC-E1. MD simulations neatly showed generally decreased stability (increased flexibility) of all variants with respect to the WT heterotetramer, particularly in the TPP binding region. These results are discussed in light of disease severity of the patients bearing such mutations and highlight the difficulty of developing chaperone-based therapies for PDC deficiency. © 2021 Elsevier B.V. and Société Française de Biochimie et Biologie Moléculaire (SFBBM)},
	keywords = {protein aggregation; Protein misfolding; inborn errors of metabolism; MISSENSE MUTATIONS; Pyruvate dehydrogenase complex deficiency; Cofactor affinity},
	year = {2021},
	eissn = {1638-6183},
	pages = {78-88}
}

@article{MTMT:30672811,
	title = {Redox-Driven Signaling: 2-Oxo Acid Dehydrogenase Complexes as Sensors and Transmitters of Metabolic Imbalance},
	url = {https://m2.mtmt.hu/api/publication/30672811},
	author = {Bunik, Victoria I.},
	doi = {10.1089/ars.2017.7311},
	journal-iso = {ANTIOXID REDOX SIGNAL},
	journal = {ANTIOXIDANTS & REDOX SIGNALING},
	volume = {30},
	unique-id = {30672811},
	issn = {1523-0864},
	abstract = {Significance: This article develops a holistic view on production of reactive oxygen species (ROS) by 2-oxo acid dehydrogenase complexes.Recent Advances: Catalytic and structural properties of the complexes and their components evolved to minimize damaging effects of side reactions, including ROS generation, simultaneously exploiting the reactions for homeostatic signaling.Critical Issues: Side reactions of the complexes, characterized in vitro, are analyzed in view of protein interactions and conditions in vivo. Quantitative data support prevalence of the forward 2-oxo acid oxidation over the backward NADH oxidation in feeding physiologically significant ROS production by the complexes. Special focus on interactions between the active sites within 2-oxo acid dehydrogenase complexes highlights the central relevance of the complex-bound thiyl radicals in regulation of and signaling by complex-generated ROS. The thiyl radicals arise when dihydrolipoyl residues of the complexes regenerate FADH(2) from the flavin semiquinone coproduced with superoxide anion radical in 1e(-) oxidation of FADH(2) by molecular oxygen.Future Directions: Interaction of 2-oxo acid dehydrogenase complexes with thioredoxins (TRXs), peroxiredoxins, and glutaredoxins mediates scavenging of the thiyl radicals and ROS generated by the complexes, underlying signaling of disproportional availability of 2-oxo acids, CoA, and NAD(+) in key metabolic branch points through thiol/disulfide exchange and medically important hypoxia-inducible factor, mammalian target of rapamycin (mTOR), poly (ADP-ribose) polymerase, and sirtuins. High reactivity of the coproduced ROS and thiyl radicals to iron/sulfur clusters and nitric oxide, peroxynitrite reductase activity of peroxiredoxins and transnitrosylating function of thioredoxin, implicate the side reactions of 2-oxo acid dehydrogenase complexes in nitric oxide-dependent signaling and damage.},
	keywords = {PEROXIDE; NITROSYLATION; thioredoxin; cellular defense; lipoate; 2-oxo acid dehydrogenase},
	year = {2019},
	eissn = {1557-7716},
	pages = {1911-1947}
}

@article{MTMT:31566924,
	title = {Enzyme-encapsulating polymeric nanoparticles: A potential adjunctive therapy in Pseudomonas aeruginosa biofilm-associated infection treatment},
	url = {https://m2.mtmt.hu/api/publication/31566924},
	author = {Han, Chendong and Goodwine, James and Romero, Nicholas and Steck, Kyle S. and Sauer, Karin and Doiron, Amber},
	doi = {10.1016/j.colsurfb.2019.110512},
	journal-iso = {COLLOID SURFACE B},
	journal = {COLLOIDS AND SURFACES B: BIOINTERFACES},
	volume = {184},
	unique-id = {31566924},
	issn = {0927-7765},
	abstract = {Pseudomonas aeruginosa is a pathogen known to be associated with a variety of diseases and conditions such as cystic fibrosis, chronic wound infections, and burn wound infections. A novel approach was developed to combat the problem of biofilm antibiotic tolerance by reverting biofilm bacteria back to the planktonic mode of growth. This reversion was achieved through the enzymatic depletion of available pyruvate using pyruvate dehydrogenase, which induced biofilm bacteria to disperse from the surface-associated mode of growth into the surrounding environment. However, direct use of the enzyme in clinical settings is not practical as the enzyme is susceptible to denaturation under various storage conditions. We hypothesize that by encapsulating pyruvate dehydrogenase into degradable, biocompatible poly(lactic-co-glycolic) acid nanoparticles, the activity of the enzyme can be extended to deplete available pyruvate and induce dispersion of mature Pseudomonas aeruginosa biofilms. Several particle formulations were attempted in order to permit the use of the smallest dose of nanoparticles while maintaining pyruvate dehydrogenase activity for an extended time length. The nanoparticles synthesized using the optimal formulation showed an average size of 266.7 +/- 1.8 nm. The encapsulation efficiency of pyruvate dehydrogenase was measured at 17.9 +/- 1.4%. Most importantly, the optimal formulation dispersed biofilms and exhibited enzymatic activity after being stored at 37 degrees C for 6 days.},
	keywords = {Drug delivery; PLGA; Enzyme immobilization; Poly(actic-co-glycolic) acid},
	year = {2019},
	eissn = {1873-4367},
	orcid-numbers = {Doiron, Amber/0000-0002-6963-0989}
}

@book{MTMT:27132991,
	title = {Vitamin-dependent multienzyme complexes of 2-oxo acid dehydrogenases: Structure, function, regulation and medical implications},
	url = {https://m2.mtmt.hu/api/publication/27132991},
	isbn = {9781536121889},
	author = {Artiukhov, A and Bunik, V},
	publisher = {Nova Science Publishers Inc.; Nova Publishers},
	unique-id = {27132991},
	year = {2017}
}

@article{MTMT:24453783,
	title = {Pyruvate dehydrogenase complex (PDC) export from the mitochondrial matrix},
	url = {https://m2.mtmt.hu/api/publication/24453783},
	author = {Ng, F and Tang, BL},
	doi = {10.3109/09687688.2014.987183},
	journal-iso = {MOL MEMBR BIOL},
	journal = {MOLECULAR MEMBRANE BIOLOGY},
	volume = {31},
	unique-id = {24453783},
	issn = {0968-7688},
	year = {2014},
	eissn = {1464-5203},
	pages = {207-210}
}

@article{MTMT:24131865,
	title = {A nuclear pyruvate dehydrogenase complex is important for the generation of Acetyl-CoA and histone acetylation},
	url = {https://m2.mtmt.hu/api/publication/24131865},
	author = {Sutendra, G and Kinnaird, A and Dromparis, P and Paulin, R and Stenson, TH and Haromy, A and Hashimoto, K and Zhang, N and Flaim, E and Michelakis, ED},
	doi = {10.1016/j.cell.2014.04.046},
	journal-iso = {CELL},
	journal = {CELL},
	volume = {158},
	unique-id = {24131865},
	issn = {0092-8674},
	year = {2014},
	eissn = {1097-4172},
	pages = {84-97}
}

@article{MTMT:21254142,
	title = {Roles of dihydrolipoamide dehydrogenase Lpd1 in Candida albicans filamentation},
	url = {https://m2.mtmt.hu/api/publication/21254142},
	author = {Kim, SY Kim J},
	doi = {10.1016/j.fgb.2010.06.005},
	journal-iso = {FUNGAL GENET BIOL},
	journal = {FUNGAL GENETICS AND BIOLOGY},
	volume = {47},
	unique-id = {21254142},
	issn = {1087-1845},
	year = {2010},
	eissn = {1096-0937},
	pages = {782-789}
}

@{MTMT:10038476,
	title = {Cytadherence and the Cytoskeleton},
	url = {https://m2.mtmt.hu/api/publication/10038476},
	author = {Balish, MF and Krause, DC},
	booktitle = {Molecular Biology and Pathogenicity of Mycoplasmas 2002},
	unique-id = {10038476},
	year = {2002},
	pages = {491-518}
}

@article{MTMT:1003011,
	title = {Autoantibodies against subunits of pyruvate dehydrogenase and citrate synthase in a case of paediatric biliary cirrhosis},
	url = {https://m2.mtmt.hu/api/publication/1003011},
	author = {Melegh, Béla and Skuta, G and Pajor, László and Hegedus, G and Sümegi, Balázs},
	doi = {10.1136/gut.42.5.753},
	journal-iso = {GUT},
	journal = {GUT},
	volume = {42},
	unique-id = {1003011},
	issn = {0017-5749},
	year = {1998},
	eissn = {1468-3288},
	pages = {753-756}
}

@article{MTMT:20173391,
	title = {PURIFICATION, CHARACTERIZATION AND LOCALIZATION OF MITOCHONDRIAL DIHYDROOROTATE DEHYDROGENASE IN PLASMODIUM-FALCIPARUM, HUMAN MALARIA PARASITE},
	url = {https://m2.mtmt.hu/api/publication/20173391},
	author = {Krungkrai, J},
	doi = {10.1016/0304-4165(94)00158-T},
	journal-iso = {BBA-GEN SUBJECTS},
	journal = {BIOCHIMICA ET BIOPHYSICA ACTA-GENERAL SUBJECTS},
	volume = {1243},
	unique-id = {20173391},
	issn = {0304-4165},
	year = {1995},
	eissn = {1872-8006},
	pages = {351-360}
}

@article{MTMT:22861805,
	title = {Immobilized enzymes as tools for the demonstration of metabolon formation. A short overview},
	url = {https://m2.mtmt.hu/api/publication/22861805},
	author = {Sonia, Beeckmans and Edilbert, Van Driessche and Louis, Kanarek},
	doi = {10.1002/jmr.300060408},
	journal-iso = {J MOL RECOGNIT},
	journal = {JOURNAL OF MOLECULAR RECOGNITION},
	volume = {6},
	unique-id = {22861805},
	issn = {0952-3499},
	year = {1993},
	eissn = {1099-1352},
	pages = {195-204}
}

@article{MTMT:20173070,
	title = {THE SECRETORY S-COMPLEX IN BACILLUS-SUBTILIS IS IDENTIFIED AS PYRUVATE-DEHYDROGENASE},
	url = {https://m2.mtmt.hu/api/publication/20173070},
	author = {Hemila, H and Palva, A and Paulin, L and Adler, L and Arvidson, S and Palva, I},
	doi = {10.1016/0923-2508(91)90055-F},
	journal-iso = {RES MICROBIOL},
	journal = {RESEARCH IN MICROBIOLOGY},
	volume = {142},
	unique-id = {20173070},
	issn = {0923-2508},
	year = {1991},
	eissn = {1769-7123},
	pages = {779-785}
}

@article{MTMT:20173394,
	title = {APPLICATION OF HIGH-PERFORMANCE LIQUID-CHROMATOGRAPHY TO THE PURIFICATION, DISINTEGRATION AND MOLECULAR MASS DETERMINATION OF PYRUVATE-DEHYDROGENASE MULTIENZYME COMPLEXES FROM DIFFERENT SOURCES},
	url = {https://m2.mtmt.hu/api/publication/20173394},
	author = {Maas, E and Adami, P and Bisswanger, H},
	doi = {10.1016/0021-9673(90)85041-S},
	journal-iso = {J CHROMATOGR A},
	journal = {JOURNAL OF CHROMATOGRAPHY A},
	volume = {521},
	unique-id = {20173394},
	issn = {0021-9673},
	year = {1990},
	eissn = {1873-3778},
	pages = {169-178}
}

@article{MTMT:20173393,
	title = {LOCALIZATION OF THE ALPHA-OXOACID DEHYDROGENASE MULTIENZYME COMPLEXES WITHIN THE MITOCHONDRION},
	url = {https://m2.mtmt.hu/api/publication/20173393},
	author = {Maas, E and Bisswanger, H},
	doi = {10.1016/0014-5793(90)80840-F},
	journal-iso = {FEBS LETT},
	journal = {FEBS LETTERS},
	volume = {277},
	unique-id = {20173393},
	issn = {0014-5793},
	year = {1990},
	eissn = {1873-3468},
	pages = {189-190}
}

@article{MTMT:1322375,
	title = {CYTOCHROME-OXIDASE DEFICIENCY AFFECTING THE STRUCTURE OF THE MYOFIBER AND THE SHAPE OF MITOCHONDRIAL-CRISTAE MEMBRANE},
	url = {https://m2.mtmt.hu/api/publication/1322375},
	author = {Sümegi, Balázs and Melegh, Béla and Adamovich, Károly and Trombitás, Károly},
	doi = {10.1016/0009-8981(90)90266-U},
	journal-iso = {CLIN CHIM ACTA},
	journal = {CLINICA CHIMICA ACTA},
	volume = {192},
	unique-id = {1322375},
	issn = {0009-8981},
	abstract = {Cytochrome oxidase deficiency was detected in the skeletal muscle of a newborn floppy child. There was a significant decrease in the quantity of subunit 5 and 6 of cytochrome oxidase as showed in Western blot with cytochrome oxidase antibody. By contrast, the NADH: cytochrome c oxidoreductase activity was normal. Electron microscopic studies revealed serious distortion in the myofibres with broken Z-bands and disorganized fibers. The relative molecular mass of actin in the myopathic muscle was smaller than in control. The diffuse actin band in Western blot suggested a proteolytic degradation of F-actin in the myopathic muscle. There was also a serious distortion in the mitochondrial structure. Cytochrome oxidase has a direct role in the formation of cristae and mutation in its components may be directly responsible for the abnormal structure.},
	year = {1990},
	eissn = {1873-3492},
	pages = {9-18}
}