Search for other papers by NG Krylova in
Current site
Google Scholar
PubMed
Search for other papers by TA Kulahava in
Current site
Google Scholar
PubMed
Search for other papers by VT Cheschevik in
Current site
Google Scholar
PubMed
Search for other papers by IK Dremza in
Current site
Google Scholar
PubMed
Search for other papers by GN Semenkova in
Current site
Google Scholar
PubMed
Search for other papers by IB Zavodnik in
Current site
Google Scholar
PubMed
Quinones are among the rare compounds successfully used as therapeutic agents to correct mitochondrial diseases and as specific regulators of mitochondrial function within cells. The aim of the present study was to elucidate the redox-dependent effects of quinones on mitochondrial function. The functional parameters [respiratory activity, membrane potential, and reactive oxygen species (ROS) generation] of isolated rat liver mitochondria and mitochondria in intact cells were measured in the presence of eight exogenously applied quinones that differ in lipophilicity and one-electron reduction potential. The quinones affected the respiratory parameters of mitochondria, and dissipated the mitochondrial membrane potential as well as influenced (either decreased or enhanced) ROS generation, and restored the electron flow during electron transport chain inhibition. The stimulation of ROS production by juglone and 2,5-di-tert-butyl-1,4-benzoquinone was accompanied by a decrease in the acceptor control and respiration control ratios, dissipation of the mitochondrial membrane potential and induction of the reverse electron flow under succinate oxidation in isolated mitochondria. Menadione and 2,3,5-trimethyl-1,4-benzoquinone, which decreased the mitochondrial ROS generation, did not affect the mitochondrial potential and, vice versa, were capable of restoring electron transport during Complex I inhibition. In intact C6 cells, all the quinones, except for coenzyme Q10, decreased the mitochondrial membrane potential. Juglone, 1,4-benzoquinone, and menadione showed the most pronounced effects. These findings indicate that quinones with the reduction potential values E1/2 in the range from −99 to −260 mV were effective redox regulators of mitochondrial electron transport.
-
1.
Adams R , Bachmann WE , Fieser LF , Blatt AH , Johnson JR (1948): Organic Reactions. John Wiley, New York, NY, USA
-
2.
Akerman KE : Qualitative measurements of the mitochondrial membrane potential in situ in Ehrlich ascites tumour cells using the safranin method. Biochim. Biophys. Acta 546, 341–347 (1979)
-
3.
Andreyev AY , Kushnareva YE , Starkov AA : Mitochondrial metabolism of reactive oxygen species. Biochemistry (Mosc.) 70, 200–214 (2005)
-
4.
Brand MD : The sites and topology of mitochondrial superoxide production. Exp. Gerontol. 45, 466–472 (2010)
-
5.
Briere JJ , Schlemmer D , Chretien D , Rustin P : Quinone analogues regulate mitochondrial substrate competitive oxidation. Biochem. Biophys. Res. Commun. 316, 1138–1142 (2004)
-
6.
Brunmark A , Cadenas E : Redox and addition chemistry of quinoid compounds and its biological implications. Free Radic. Biol. Med. 7, 435–477 (1989)
-
7.
Buffinton GD , Ollinger K , Brunmark A , Cadenas E : DT-diaphorase-catalysed reduction of 1, 4-naphthoquinone derivatives and glutathionyl-quinone conjugates. Effect of substituents on autoxidation rates. Biochem. J. 257, 561–571 (1989)
-
8.
Cathcart R , Schwiers E , Ames BN : Detection of picomole levels of hydroperoxides using a fluorescent dichlorofluorescein assay. Anal. Biochem. 134, 111–116 (1983)
-
9.
Chan TS , Teng S , Wilson JX , Galati G , Khan S , O’Brien PJ : Coenzyme Q cytoprotective mechanisms for mitochondrial Complex I cytopathies involves NAD(P)H: quinone oxidoreductase 1 (NQO1). Free Radic. Res. 36, 421–427 (2002)
-
10.
Chan TS , Wilson JX , O’Brien PJ : Coenzyme Q cytoprotective mechanisms. Methods Enzymol. 382, 89–104 (2004)
-
11.
Chen M , Liu B , Gu L , Zhu Q : The effect of ring substituents on the mechanism of interaction of exogenous quinones with the mitochondrial respiratory chain. Biochim. Biophys. Acta 851, 469–474 (1986)
-
12.
Chen Q , Vazquez EJ , Moghaddas S , Hoppel CL , Lesnafsky EJ : Production of reactive oxygen species by mitochondria. Central role of complex III. J. Biol. Chem. 278, 36027–36031 (2003)
-
13.
Connover TE , Ernster L : DT diaphorase. II. Relation to respiratory chain of intact mitochondria. Biochim. Biophys. Acta 58, 189–192 (1962)
-
14.
Deller S , Macheroux P , Sollner S : Flavin-dependent quinone reductases. Cell. Mol. Life Sci. 65, 141–160 (2008)
-
15.
de Vries S , Berden JA , Slater EC : Properties of a semiquinone anion located in the QH2:cytochrome c oxidoreductase segment of the mitochondrial respiratory chain. FEBS Lett. 122, 143–148 (1980)
-
16.
Dremza IK , Lapshina EA , Kujawa J , Zavodnik IB : Oxygen-related processes in red blood cells exposed to tert-butyl hydroperoxide. Redox Rep. 11, 185–192 (2006)
-
17.
Fagian M , Pereira-da-Silva L , Martins IS , Vercesi AE : Membrane protein thiol cross-linking associated with the permeabilization of the inner mitochondrial membrane by Ca2+ plus prooxidants. J. Biol. Chem. 265, 1955–1960 (1990)
-
18.
Fieser LF , Fieser M (1968): Reagents for Organic Synthesis. John Wiley, New York, NY, USA
-
19.
Flaig W , Ploetz T , Biergans H : Information on humic acids. Report on the formation and reactions of some hydroxyquinones. Justus Liebigs Ann. Chem. 597, 196–213 (1956)
-
20.
Gerasimenko JV , Gerasimenko OV , Palejwala A , Tepikin AV , Petersen OH , Watson AJ : Menadione-induced apoptosis: roles of cytosolic Ca2+ elevations and the mitochondrial permeability transition pore. J. Cell. Sci. 115, 485–497 (2002)
-
21.
Giorgio V , Petronilli V , Ghelli A , Carelli V , Rugolo M , Lenaz G , Bernardi P : The effects of idebenone on mitochondrial bioenergetics. Biochim. Biophys. Acta 1817, 363–369 (2012)
-
22.
Gomes A , Fernandes E , Lima JL : Fluorescence probes used for detection of reactive oxygen species. J. Biochem. Biophys. Methods 65, 45–80 (2005)
-
23.
Haefeli RH , Erb M , Gemperli AC , Robay D , Courdier FI , Anklin C , Dallmann R , Gueven N : NQO1-Dependent redox cycling of idebenone: effects on cellular redox potential and energy levels. PLoS One 6, e17963 (2011)
-
24.
Henry TR , Wallace KB : Differential mechanisms of induction of the mitochondrial permeability transition by quinones of varying chemical reactivities. Toxicol. Appl. Pharmacol. 134, 195–203 (1995)
-
25.
Jastroch M , Divakaruni AS , Mookerjee S , Treberg JR , Brand MD : Mitochondrial proton and electron leaks. Essays Biochem. 47, 53–67 (2010)
-
26.
Ji Y , Qu Z , Zou X : Juglone-induced apoptosis in human gastric cancer SGC-7901 cells via the mitochondrial pathway. Exp. Toxicol. Pathol. 63, 69–78 (2011)
-
27.
Johnson D , Lardy HA : Isolation of liver or kidney mitochondria. Methods Enzymol. 10, 94–96 (1967)
-
28.
Kelso GF , Porteous CM , Coulter CV , Hughes G , Porteous WK , Ledgerwood EC , Smith RA , Murphy MP : Selective targeting of a redox-active ubiquinone to mitochondria within cells: antioxidant and antiapoptotic properties. J. Biol. Chem. 276, 4588–4596 (2001)
-
29.
Kruglov AG , Subbotina KB , Saris NE : Redox-cycling compounds can cause the permeabilization of mitochondrial membranes by mechanisms other than ROS production. Free Radic. Biol. Med. 44, 646–656 (2008)
-
30.
Lambert AJ , Brand MD : Inhibitors of quinone-binding site allow rapid superoxide production from mitochondrial NADH: ubiquinone oxidoreductase. J. Biol. Chem. 279, 39414–39420 (2004)
-
31.
Lenaz G : Quinone specificity of Complex I. Biochim. Biophys. Acta 1364, 207–221 (1998)
-
32.
Lenaz G : The mitochondrial production of reactive oxygen species: mechanisms and implications in human pathology. IUBMB Life 52, 159–164 (2001)
-
33.
Li N , Ragheb K , Lawler G , Sturgis J , Rajwa B , Melendez JA , Robinson JP : Mitochondrial complex I inhibitor rotenone induces apoptosis through enhancing mitochondrial reactive oxygen species production. J. Biol. Chem. 278, 8516–8525 (2003)
-
34.
Lowry OH , Rosebrough NJ , Farr AL , Randall RJ : Protein measurement with the Folin phenol reagent. J. Biol. Chem. 193, 265–275 (1951)
-
35.
Marchi S , Giorgi C , Suski JM , Agnoletto C , Bononi A , Bonora M , DeMarchi E , Missiroli S , Patergnani S , Poletti F , Rimessi A , Duszynski J , Wieckowski MR , Pinton P : Mitochondria-ROS crosstalk in the control of cell death and aging. J. Signal Transduct. 2012, 329635 (2012)
-
36.
Moore AL , Bonner WD : Measurements of membrane potentials in plant mitochondria with the safranin method. Plant Physiol. 70, 1271–1276 (1982)
-
37.
Motovilov K , Yaguzhinsky L : Inhibitors of succinate dehydrogenase and complex III promote respiration of liver mitochondria under conditions of functioning DT-diaphorase. Biochim. Biophys. Acta 1777, S98–S99 (2008)
-
38.
Mukherjee T (2001): Radiation chemistry of quinones. In: Radiation Chemistry: Present Status and Future Trends, eds Jonah CD, Rao BSM, Elsevier Science, Amsterdam, The Netherlands, pp. 287–317
-
39.
O’Brien PJ : Molecular mechanisms of quinone cytotoxicity. Chem. Biol. Interact. 80, 1–41 (1991)
-
40.
Ollinger K , Kågedal K : Induction of apoptosis by redox-cycling quinones. Subcell. Biochem. 36, 151–170 (2002)
-
41.
Palmeira CM , Wallace KB : Benzoquinone inhibits the voltage-dependent induction of the mitochondrial permeability transition caused by redox-cycling naphthoquinones. Toxicol. Appl. Pharmacol. 143, 338–347 (1997)
-
42.
Petronilli V , Costantini P , Scorrano L , Colonna R , Passamonti S , Bernardi P : The voltage sensor of the mitochondrial permeability transition pore is tuned by oxidation-reduction state of vicinal thiols. Increase of the gating potential by oxidants and its reversal by reducing agents. J. Biol. Chem. 269, 16638–16642 (1994)
-
43.
Powis G , Appel PL : Relationship of the single-electron reduction potential of quinones to their reduction by flavoproteins. Biochem. Pharmacol. 29, 2567–2572 (1980)
-
44.
Reers M , Smith TW , Chen LB : J-aggregate formation of a carbocyanine as a quantitative fluorescent indicator of membrane potential. Biochemistry 30, 4480–4486 (1991)
-
45.
Robinson KM , Janes MS , Pehar M , Monette JS , Ross MF , Hagen TM , Murphy MP , Beckman JS : Elective fluorescent imaging of superoxide in vivo using ethidium-based probes. Proc. Natl. Acad. Sci. U S A 103, 15038–15043 (2006)
-
46.
Ruzicka FJ , Crane FL : Four quinone reduction sites in the NADH-dehydrogenase complex. Biochem. Biophys. Res. Commun. 38, 249–254 (1970)
-
47.
Ruzicka FJ , Crane FL : Quinone interaction with the respiratory chain-linked NADH-dehydrogenase of beef heart mitochondria. Juglone reductase activity. Biochim. Biophys. Acta 223, 71–85 (1970)
-
48.
Selivanov VA , Votyakova TV , Pivtoraiko VN , Zeak J , Sukhomlin T , Trucco M , Roca J , Cascante M : Reactive oxygen species production by forward and reverse electron fluxes in the mitochondrial respiratory chain. PLoS Comput. Biol. 7, e1001115 (2011)
-
49.
Shadyro OI , Glushonok GK , Glushonok TG , Edimecheva IP , Moroz AG , Sosnovskaya AA , Yurkova IL , Polozov GI : Quinones as free-radical fragmentation inhibitors in biologically important molecules. Free Radic. Res. 36, 859–867 (2002)
-
50.
Siegel G , Reigan P , Ross D (2008): One- and two-electron-mediated reduction of quinones: enzymology and toxicological implication. In: Advances in Bioactivation Research, ed Elfarra AA, Springer, New York, NY, USA, pp. 1–29
-
51.
Siraki AG , Chan TS , O’Brien P : Application of quantitative structure-toxicity relationships for the comparison of the cytotoxicity of 14 p-benzoquinone congeners in primary cultured rat hepatocytes versus PC12 cells. Toxicol. Sci. 81, 148–159 (2004)
-
52.
Swallow AJ (1982): Physical chemistry of semiquinone. In: Function of Quinones in Energy Conserving Systems, ed Trumpower B, Academic Press, New York, NY, USA, p. 71
-
53.
The PubChem Project: Databases. Available at: http://pubchem.ncbi.nlm.nih.gov. Accessed 1 May 2013
-
54.
Treberg JR , Quinlan CL , Brand MD : Evidence for two sites of superoxide production by mitochondrial NADH-ubiquinone oxidoreductase (complex I). J. Biol. Chem. 286, 27103–27110 (2011)
-
55.
Vervoort LM , Randen JE , Thijssen HH : The potent antioxidant activity of the vitamin K cycle in microsomal lipid peroxidation. Biochem. Pharmacol. 54, 871–876 (1997)
-
56.
Wrona M , Wardman P : Properties of the radical intermediate obtained on oxidation of 2′,7′-dichlorodihydrofluorescein, a probe for oxidative stress. Free Radic. Biol. Med. 41, 657–667 (2006)
Editor-in-Chief
László ROSIVALL (Semmelweis University, Budapest, Hungary)
Managing Editor
Anna BERHIDI (Semmelweis University, Budapest, Hungary)
Co-Editors
- Gábor SZÉNÁSI (Semmelweis University, Budapest, Hungary)
- Ákos KOLLER (Semmelweis University, Budapest, Hungary)
- Zsolt RADÁK (University of Physical Education, Budapest, Hungary)
- László LÉNÁRD (University of Pécs, Hungary)
- Zoltán UNGVÁRI (Semmelweis University, Budapest, Hungary)
Assistant Editors
- Gabriella DÖRNYEI (Semmelweis University, Budapest, Hungary)
- Zsuzsanna MIKLÓS (Semmelweis University, Budapest, Hungary)
- György NÁDASY (Semmelweis University, Budapest, Hungary)
Hungarian Editorial Board
- György BENEDEK (University of Szeged, Hungary)
- Zoltán BENYÓ (Semmelweis University, Budapest, Hungary)
- Mihály BOROS (University of Szeged, Hungary)
- László CSERNOCH (University of Debrecen, Hungary)
- Magdolna DANK (Semmelweis University, Budapest, Hungary)
- László DÉTÁRI (Eötvös Loránd University, Budapest, Hungary)
- Zoltán GIRICZ (Semmelweis University, Budapest, Hungary and Pharmahungary Group, Szeged, Hungary)
- Zoltán HANTOS (Semmelweis University, Budapest and University of Szeged, Hungary)
- Zoltán HEROLD (Semmelweis University, Budapest, Hungary)
- László HUNYADI (Semmelweis University, Budapest, Hungary)
- Gábor JANCSÓ (University of Pécs, Hungary)
- Zoltán KARÁDI (University of Pecs, Hungary)
- Miklós PALKOVITS (Semmelweis University, Budapest, Hungary)
- Gyula PAPP (University of Szeged, Hungary)
- Gábor PAVLIK (University of Physical Education, Budapest, Hungary)
- András SPÄT (Semmelweis University, Budapest, Hungary)
- Gyula SZABÓ (University of Szeged, Hungary)
- Zoltán SZELÉNYI (University of Pécs, Hungary)
- Lajos SZOLLÁR (Semmelweis University, Budapest, Hungary)
- József TOLDI (MTA-SZTE Neuroscience Research Group and University of Szeged, Hungary)
- Árpád TÓSAKI (University of Debrecen, Hungary)
International Editorial Board
- Dragan DJURIC (University of Belgrade, Serbia)
- Christopher H. FRY (University of Bristol, UK)
- Stephen E. GREENWALD (Blizard Institute, Barts and Queen Mary University of London, UK)
- Tibor HORTOBÁGYI (University of Groningen, Netherlands)
- George KUNOS (National Institutes of Health, Bethesda, USA)
- Massoud MAHMOUDIAN (Iran University of Medical Sciences, Tehran, Iran)
- Tadaaki MANO (Gifu University of Medical Science, Japan)
- Luis Gabriel NAVAR (Tulane University School of Medicine, New Orleans, USA)
- Hitoo NISHINO (Nagoya City University, Japan)
- Ole H. PETERSEN (Cardiff University, UK)
- Ulrich POHL (German Centre for Cardiovascular Research and Ludwig-Maximilians-University, Planegg, Germany)
- Andrej A. ROMANOVSKY (University of Arizona, USA)
- Anwar Ali SIDDIQUI (Aga Khan University, Karachi, Pakistan)
- Csaba SZABÓ (University of Fribourg, Switzerland)
- Eric VICAUT (Université de Paris, UMRS 942 INSERM, France)
Editorial Correspondence:
Physiology International
Semmelweis University
Faculty of Medicine, Institute of Translational Medicine
Nagyvárad tér 4, H-1089 Budapest, Hungary
Phone/Fax: +36-1-2100-100
E-mail: pi@semmelweis.hu
Indexing and Abstracting Services:
- Biological Abstracts
- BIOSIS Previews
- CAB Abstracts
- CABELLS Journalytics
- EMBASE/Excerpta Medica
- Global Health
- Index Copernicus
- Index Medicus
- Medline
- Referativnyi Zhurnal
- SCOPUS
- WoS - Science Citation Index Expanded
| 2023 | |
|---|---|
| Web of Science | |
| Journal Impact Factor | 2.2 |
| Rank by Impact Factor | Q3 (Physiology) |
| Journal Citation Indicator | 0.58 |
| Scopus | |
| CiteScore | 3.4 |
| CiteScore rank | Q2 (Physical Therapy, Sports Therapy and Rehabilitation) |
| SNIP | 0.508 |
| Scimago | |
| SJR index | 0.407 |
| SJR Q rank | Q2 |
| Physiology International | |
|---|---|
| Publication Model | Hybrid |
| Submission Fee | none |
| Article Processing Charge | 1100 EUR/article |
| Printed Color Illustrations | 40 EUR (or 10 000 HUF) + VAT / piece |
| Regional discounts on country of the funding agency | World Bank Lower-middle-income economies: 50% World Bank Low-income economies: 100% |
| Further Discounts | Editorial Board / Advisory Board members: 50% Corresponding authors, affiliated to an EISZ member institution subscribing to the journal package of Akadémiai Kiadó: 100% |
| Subscription fee 2025 | Online subsscription: 752 EUR / 828 USD Print + online subscription: 880 EUR / 968 USD |
| Subscription Information | Online subscribers are entitled access to all back issues published by Akadémiai Kiadó for each title for the duration of the subscription, as well as Online First content for the subscribed content. |
| Purchase per Title | Individual articles are sold on the displayed price. |
| Physiology International | |
|---|---|
| Language | English |
| Size | B5 |
| Year of Foundation |
2006 (1950) |
| Volumes per Year |
1 |
| Issues per Year |
4 |
| Founder | Magyar Tudományos Akadémia |
| Founder's Address |
H-1051 Budapest, Hungary, Széchenyi István tér 9. |
| Publisher | Akadémiai Kiadó |
| Publisher's Address |
H-1117 Budapest, Hungary 1516 Budapest, PO Box 245. |
| Responsible Publisher |
Chief Executive Officer, Akadémiai Kiadó |
| ISSN | 2498-602X (Print) |
| ISSN | 2677-0164 (Online) |
Monthly Content Usage
| Abstract Views | Full Text Views | PDF Downloads | |
|---|---|---|---|
| Jun 2024 | 80 | 0 | 0 |
| Jul 2024 | 16 | 0 | 0 |
| Aug 2024 | 34 | 0 | 0 |
| Sep 2024 | 60 | 0 | 0 |
| Oct 2024 | 136 | 0 | 0 |
| Nov 2024 | 51 | 0 | 0 |
| Dec 2024 | 3 | 0 | 0 |
Copyright Akadémiai Kiadó AKJournals is the trademark of Akadémiai Kiadó's journal publishing business branch.