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Chinopoulos Christos

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COST Action CA15203 (2016-2021): MitoEAGLE
Evolution-Age-Gender-Lifestyle-Environment: mitochondrial fitness mapping


Chinopoulos Christos


MitoPedia topics: EAGLE 

COST: Member COST WG1: WG1


COST Mentor: Mentor

MC Member - Management Committee MitoEAGLE
Name Chinopoulos Christos, MD, PhD, Associate Professor
Institution
Christos Chinopoulos

Department of Medical Biochemistry,

Semmelweis University, HU

Address Tuzolto st. 37-47, 1094
City Budapest
State/Province
Country Hungary
Email [email protected]
Weblink Christos Chinopoulos
O2k-Network Lab HU Budapest Chinopoulos C

Bioenergetics Communications

Keywords: mitochondria, oncometabolism, tumor metabolism, substrate-level phosphorylation
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NextGen-O2k

  • Prof. Christos Chinopoulos is Key Opinion Leader (KOL) in the NextGen-O2k project.

MitoEAGLE Short-Term Scientific Mission

Work Plan summary
In our laboratory we examine the contribution of mitochondrial substrate-level phosphorylation (mSLP) to ATP output and ANT directionality during true anoxia or inhibition of the electron transport chain (ETC) in isolated mitochondria or permeabilized cells. True anoxia is ensured by monitoring oxygen concentration in sealed Oroboros chambers when mitochondria respire on various substrates in the abundance of ADP. On the other hand, chemical anoxia is induced by targeted inhibition of ETC components. Under such conditions mSLP is addressed by protocols relying on membrane potential measurements using safranine O, also monitored by the O2k-Fluo LED2-Module, as described elsewhere (FASEB J. 2010, 24:2405). However, it has come to our attention that targeted inhibition of complex I perturbs mSLP even in the presence of true anoxia. Parallel to these measurements, metabolomic analysis of citricacid cycle metabolites obtained from fractions of such experiments hint on a privileged dependence of complex I activity to KGDHC. Currently, we are attempting to address this further by measuring NADH in standard fluorimetric cuvettes using home-made 3D-printed plugs in order to induce and maintain anoxia where we can also measure membrane potential by safranine O among other parameters. However, we are only partially successful, and we need to be able to measure oxygen, NADH and safranine O fluorescence in the same samples (albeit in different chambers), simultaneously. The O2k-NextGen is designed by Oroboros for achieving exactly that. The plan is to isolate mouse liver mitochondria, subject them to ADP and substrates in sealed Oroboros chambers, attain anoxia, add the ETC inhibitors and collect fractions at various time points to be evaluated by untargeted metabolomic analysis. Anoxia, NADH levels and membrane potential will be measured throughout these experiments and complement the results of the metabolomic analysis.


Participated at


Visiting scientist in the Oroboros O2k-Laboratory

O2k-Network

Christos Chinopoulos : Visiting scientist at the Oroboros O2k-Laboratory

  • December 14 to December 22 2017


Labels: Field of research: Basic  Topics: Mitochondrial mechanisms of neurodegeneration, Permeability transition pore 


Publications

 PublishedReference
Ravasz 2024 Sci Rep2024Ravasz D, Bui D, Nazarian S, Pallag G, Karnok N, Roberts J, Marzullo BP, Tennant DA, Greenwood B, Kitayev A, Hill C, KomlĂłdi T, Doerrier C, Cunatova K, Fernandez-Vizarra E, Gnaiger E, Kiebish Michael A, Raska A, Kolev K, Czumbel B, Narain NR, Seyfried TN, Chinopoulos C (2024) Residual Complex I activity and amphidirectional Complex II operation support glutamate catabolism through mtSLP in anoxia. Sci Rep 14:1729. https://doi.org/10.1038/s41598-024-51365-4
Pallag 2022 Int J Mol Sci2022Pallag G, Nazarian S, Ravasz D, Bui D, KomlĂłdi T, Doerrier C, Gnaiger E, Seyfried TN, Chinopoulos C (2022) Proline oxidation supports mitochondrial ATP production when Complex I is inhibited. https://doi.org/10.3390/ijms23095111
Horvath 2022 Antioxidants (Basel)2022Horvåth G, Svåb G, Komlódi T, Ravasz D, Kacsó G, Doczi J, Chinopoulos C, Ambrus A, Tretter L (2022) Reverse and forward electron flow-induced H2O2 formation is decreased in α-ketoglutarate dehydrogenase (α-KGDH) subunit (E2 or E3) heterozygote knock out animals. https://doi.org/10.3390/antiox11081487
Hierro-Yap 2021 J Biol Chem2021Hierro-Yap C, Ć ubrtovĂĄ K, Gahura O, Panicucci B, Dewar C, Chinopoulos C, Schnaufer A, ZĂ­kovĂĄ A (2021) Bioenergetic consequences of FoF1-ATP synthase/ATPase deficiency in two life cycle stages of Trypanosoma brucei. J Biol Chem 296:100357.
Thoral 2021 Biol Lett2021Thoral E, Roussel D, Chinopoulos C, Teulier L, Salin K (2021) Low oxygen levels can help to prevent the detrimental effect of acute warming on mitochondrial efficiency in fish. Biol Lett 17:20200759.
Sarkadi 2020 Cancers (Basel)2020Sarkadi B, Meszaros K, Krencz I, Canu L, Krokker L, Zakarias S, Barna G, Sebestyen A, Papay J, Hujber Z, Butz H, Darvasi O, Igaz P, Doczi J, Luconi M, Chinopoulos C, Patocs A (2020) Glutaminases as a novel target for SDHB-associated pheochromocytomas/paragangliomas. Cancers (Basel) 12:E599.
BEC 2020.1 doi10.26124bec2020-0001.v12020Gnaiger E et al ― MitoEAGLE Task Group (2020) Mitochondrial physiology. Bioenerg Commun 2020.1. https://doi.org/10.26124/bec:2020-0001.v1
Dobolyi 2020 Brain Struct Funct2020Dobolyi A, Bago A, Palkovits M, Nemeria NS, Jordan F, Doczi J, Ambrus A, Adam-Vizi V, Chinopoulos C (2020) Exclusive neuronal detection of KGDHC-specific subunits in the adult human brain cortex despite pancellular protein lysine succinylation. Brain Struct Funct 225:639-67.
Chinopoulos 2019 Int J Biochem Cell Biol2019Chinopoulos C (2019) Succinate in ischemia: Where does it come from? Int J Biochem Cell Biol 115:105580. https://doi.org/10.1016/j.biocel.2019.105580
Salin 2018 Funct Ecol2018Salin K, Villasevil EM, Anderson GJ, Auer SK, Selman C, Hartley RC, Mullen W, Chinopoulos C, Metcalfe NB (2018) Decreased mitochondrial metabolic requirements in fasting animals carry an oxidative cost. Funct Ecol DOI: 10.1111/1365-2435.13125.
Ravasz 2018 Biochim Biophys Acta2018Ravasz D, Kacso G, Fodor V, Horvath K, Adam-Vizi V, Chinopoulos C (2018) Reduction of 2-methoxy-1,4-naphtoquinone by mitochondrially-localized Nqo1 yielding NAD+ supports substrate-level phosphorylation during respiratory inhibition. Biochim Biophys Acta 1859:909-24.
Salin 2018 Integr Comp Biol2018Salin K, Villasevil EM, Anderson GJ, Selman C, Chinopoulos C, Metcalfe NB (2018) The RCR and ATP/O indices can give contradictory messages about mitochondrial efficiency. Integr Comp Biol 58:486-94.
Ravasz 2017 Neurochem Int2017Ravasz D, Kacso G, Fodor V, Horvath K, Adam-Vizi V, Chinopoulos C (2017) Catabolism of GABA, succinic semialdehyde or gamma-hydroxybutyrate through the GABA shunt impair mitochondrial substrate-level phosphorylation. Neurochem Int 109:41-53.
Nemeth 2016 FASEB J2016Németh B, Doczi J, Csete D, Kacso G, Ravasz D, Adams D, Kiss G, Nagy AM, Horvath G, Tretter L, Mócsai A, Csépånyi-Kömi R, Iordanov I, Adam-Vizi V, Chinopoulos C (2016) Abolition of mitochondrial substrate-level phosphorylation by itaconic acid produced by LPS-induced Irg1 expression in cells of murine macrophage lineage. FASEB J 30:286-300.
Kacso 2016 Biochem J2016Kacso G, Ravasz D, Doczi J, NĂ©meth B, Madgar O, Saada A, Ilin P, Miller C, Ostergaard E, Iordanov I, Adams D, Vargedo Z, Araki M, Araki K, Nakahara M, Ito H, GĂĄl A, MolnĂĄr MJ, Nagy Z, Patocs A, Adam-Vizi V, Chinopoulos C (2016) Two transgenic mouse models for ÎČ-subunit components of succinate-CoA ligase yielding pleiotropic metabolic alterations. Biochem J 473:3463-85.
Salin 2016 Physiol Rep2016Salin K, Villasevil EM, Auer SK, Anderson GJ, Selman C, Metcalfe NB, Chinopoulos C (2016) Simultaneous measurement of mitochondrial respiration and ATP production in tissue homogenates and calculation of effective P/O ratios. Physiol Rep 10.14814/phy2.13007.
Tretter 2016 Biochim Biophys Acta2016Tretter L, Patocs A, Chinopoulos C (2016) Succinate, an intermediate in metabolism, signal transduction, ROS, hypoxia, and tumorigenesis. https://doi.org/10.1016/j.bbabio.2016.03.012
Kiss 2014 FASEB J2014Kiss G, Konrad C, Pour-Ghaz I, Mansour JJ, NĂ©meth B, Starkov AA, Adam-Vizi V, Chinopoulos C (2014) Diaphorases provide NAD+ in anoxia. FASEB J 28:1682-97.
Chinopoulos 2014 Methods Enzymol2014Chinopoulos C, Kiss G, Kawamata H, Starkov AA (2014) Measurement of ADP-ATP exchange in relation to mitochondrial transmembrane potential and oxygen consumption. Methods Enzymol 542:333-48. doi:10.1016/B978-0-12-416618-9.00017-0
Chinopoulos 2013 J Neurosci Res2013Chinopoulos C (2013) Which way does the citric acid cycle turn during hypoxia? The critical role of α-ketoglutarate dehydrogenase Complex. J Neurosci Res 91:1030-43.
Kiss 2013 FASEB J2013Kiss G, Konrad C, Doczi J, Starkov AA, Kawamata H, Manfredi G, Zhang SF, Gibson GE, Beal MF, Adam-Vizi V, Chinopoulos C (2013) The negative impact of alpha-ketoglutarate dehydrogenase complex deficiency on matrix substrate-level phosphorylation. FASEB J 27:2392-406.
Konrad 2012 PLoS One2012Konrad C, Kiss G, Torocsik B, Adam-Vizi V, Chinopoulos C (2012) Absence of Ca2+-induced mitochondrial permeability transition but presence of bongkrekate-sensitive nucleotide exchange in C. crangon and P. serratus. PLoS One 7:e39839.
Chinopoulos 2011 Methods Mol Biol2011Chinopoulos C, Zhang SF, Thomas B, Ten V, Starkov AA (2011) Isolation and functional assessment of mitochondria from small amounts of mouse brain tissue. Methods Mol Biol 793:311-24.
Chinopoulos 2011 J Neurosci Res2011Chinopoulos C (2011) The "B space" of mitochondrial phosphorylation. J Neurosci Res 89:1897-904.
Chinopoulos 2010 FASEB J2010Chinopoulos C, Gerencser AA, Mandi M, Mathe K, Töröcsik B, Doczi J, Turiak L, Kiss G, Konràd C, Vajda S, Vereczki V, Oh RJ, Adam-Vizi V (2010) Forward operation of adenine nucleotide translocase during F0F1-ATPase reversal: critical role of matrix substrate-level phosphorylation. FASEB J 24:2405-16.
Metelkin 2009 FEBS J2009Metelkin E, Demin O, KovĂĄcs Z,Chinopoulos C (2009) Modeling of ATP-ADP steady-state exchange rate mediated by the adenine nucleotide translocase in isolated mitochondria. FEBS J 276:6942-55.
Vajda 2009 FEBS J2009Vajda S, MĂĄndi M, KonrĂ d C, Kiss G, Ambrus A, Adam-Vizi V, Chinopoulos C (2009) A re-evaluation of the role of matrix acidification in uncoupler-induced Ca2+ release from mitochondria. FEBS J 276:2713-24.
Chinopoulos 20092009Chinopoulos C, Vajda S, Csanady L, Mandi M, Mathe K, Adam-Vizi V (2009) A Novel Kinetic Assay of Mitochondrial ATP-ADP Exchange Rate Mediated by the ANT. Biophys J 96, 2490-504. doi:10.1016/j.bpj.2008.12.3915

Abstracts

 PublishedReference
Pallag 2022 Abstract Bioblast2022P06.
Pallag Gergely
Pallag Gergely, Nazarian S, Ravasz D, Bui D, KomlĂłdi T, Doerrier C, Gnaiger E, Seyfried TN, Chinopoulos C (2022) Proline oxidation supports mitochondrial ATP production when Complex I is inhibited. Bioblast 2022: BEC Inaugural Conference. In: https://doi.org/10.26124/bec:2022-0001
»MitoFit Preprint«
Ravasz 2019 Abstract IOC1412019Ravasz D, Bui D, Kitayev A, Greenwood B, Hill C, Komlodi T, Doerrier C, Ozohanics O, Moore AL, Gnaiger E, Kiebish M, Kolev K, Seyfried TN, Willis WT, Narain N, Adam-Vizi V, Chinopoulos C (2019) Endogenous quinones sustain a moderate NADH oxidation by Complex I during anoxia. Mitochondr Physiol Network 24.02.
Komlodi 2018b EBEC20182018Endogenous quinones sustain NADH oxidation by Complex I during anoxia, supporting substrate-level phosphorylation in mouse liver mitochondria.
Ravasz 2018 Abstract The evolving concept of mitochondria2018Vast pools of endogenous quinones sustain NADH oxidation by Complex I during anoxia, supporting substrate-level phosphorylation in mouse liver mitochondria.
Chinopoulos 2018 MiP20182018
Christos Chinopoulos
Exclusive neuronal expression of KGDHC-specific subunits in the adult human brain cortex despite pancellular protein lysine succinylation.
Chinopoulos 2012 Abstract Bioblast2012Dobolyi A, Ostergaard E, Bago AG, Palkovits M, Adam-Vizi V, Chinopoulos C (2012) Exclusive neuronal expression of SUCLA2 in the human brain. Mitochondr Physiol Network 17.12.
Kiss 2012 Abstract Bioblast2012Kiss G, Konrad C, Doczi J, Starkov AA, Kawamata H, Manfredi G, Zhang SF, Gibson GE, Beal MF, Adam-Vizi V, Chinopoulos C (2012) The negative impact of alpha-ketoglutarate dehydrogenase complex deficiency on matrix substrate-level phosphorylation. Mitochondr Physiol Network 17.12.
Konrad 2012 Abstract Bioblast2012Konrad C, Kiss G, Torocsik B, Adam-Vizi V, Chinopoulos C (2012) Absence of Ca2+-induced mitochondrial permeability transition but presence of bongkrekate-sensitive nucleotide exchange in C. crangon and P. serratus. Mitochondr Physiol Network 17.12.
Chinopoulos C 2012 Abstract Bioblast2012Doczi J, Aniko Gal A, Echaniz-Laguna A, Mousson de Camaret B, Molnar MJ, Adam-Vizi V Chinopoulos C (2012) Properties of the mitochondrial permeability transition in human cells lacking the adenine nucleotide translocase isoform 1. Mitochondr Physiol Network 17.12.