Physiologic Implications of Reactive Oxygen Species Production by Mitochondrial Complex I Reverse Electron Transport
Abstract
:1. Introduction
2. Complex I ROS Generation
2.1. Complex I Function and ROS Production
2.2. Protonmotive Force (Δp) and Complex I ROS
2.3. Redox Ratios and Complex I ROS
3. Mitochondrial Complex I Reverse Electron Transfer (RET)
4. Detecting and Modulating RET ROS Generation
4.1. Detecting RET
4.2. Modulating RET
5. RET Generated ROS in Pathology
6. RET Generated ROS in Physiology
7. Conclusions and Future Directions
Author Contributions
Funding
Acknowledgments
Conflicts of Interest
References
- Adam-Vizi, V.; Chinopoulos, C. Bioenergetics and the formation of mitochondrial reactive oxygen species. Trends Pharmacol. Sci. 2006, 27, 639–645. [Google Scholar] [CrossRef] [PubMed]
- Murphy, M.P. How mitochondria produce reactive oxygen species. Biochem. J. 2009, 417, 1–13. [Google Scholar] [CrossRef] [PubMed]
- Cadenas, E.; Davies, K.J. Mitochondrial free radical generation, oxidative stress, and aging. Free Radic. Biol. Med. 2000, 29, 222–230. [Google Scholar] [CrossRef]
- Radi, R.; Turrens, J.F.; Chang, L.Y.; Bush, K.M.; Crapo, J.D.; Freeman, B.A. Detection of catalase in rat heart mitochondria. J. Biol. Chem. 1991, 266, 22028–22034. [Google Scholar] [PubMed]
- Salvi, M.; Battaglia, V.; Brunati, A.M.; La Rocca, N.; Tibaldi, E.; Pietrangeli, P.; Marcocci, L.; Mondovi, B.; Rossi, C.A.; Toninello, A. Catalase takes part in rat liver mitochondria oxidative stress defense. J. Biol. Chem. 2007, 282, 24407–24415. [Google Scholar] [CrossRef] [PubMed]
- Imai, H.; Nakagawa, Y. Biological significance of phospholipid hydroperoxide glutathione peroxidase (PHGPx, GPx4) in mammalian cells. Free Radic. Biol. Med. 2003, 34, 145–169. [Google Scholar] [CrossRef]
- Chen, Y.R.; Zweier, J.L. Cardiac mitochondria and reactive oxygen species generation. Circ. Res. 2014, 114, 524–537. [Google Scholar] [CrossRef] [PubMed]
- Finkel, T. Signal transduction by reactive oxygen species. J. Cell Biol. 2011, 194, 7–15. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Schieber, M.; Chandel, N.S. ROS function in redox signaling and oxidative stress. Curr. Biol. 2014, 24, R453–R462. [Google Scholar] [CrossRef] [PubMed]
- Gao, L.; Gonzalez-Rodriguez, P.; Ortega-Saenz, P.; Lopez-Barneo, J. Redox signaling in acute oxygen sensing. Redox Biol. 2017, 12, 908–915. [Google Scholar] [CrossRef] [PubMed]
- Lopez-Barneo, J.; Gonzalez-Rodriguez, P.; Gao, L.; Fernandez-Aguera, M.C.; Pardal, R.; Ortega-Saenz, P. Oxygen sensing by the carotid body: Mechanisms and role in adaptation to hypoxia. Am. J. Physiol. Cell Physiol. 2016, 310, C629–C642. [Google Scholar] [CrossRef] [PubMed]
- Scialo, F.; Fernandez-Ayala, D.J.; Sanz, A. Role of Mitochondrial Reverse Electron Transport in ROS Signaling: Potential Roles in Health and Disease. Front. Physiol. 2017, 8, 428. [Google Scholar] [CrossRef] [PubMed]
- Di Meo, S.; Reed, T.T.; Venditti, P.; Victor, V.M. Harmful and Beneficial Role of ROS. Oxid. Med. Cell. Longev. 2016, 2016, 7909186. [Google Scholar] [CrossRef] [PubMed]
- Turrens, J.F. Mitochondrial formation of reactive oxygen species. J. Physiol. 2003, 552, 335–344. [Google Scholar] [CrossRef] [PubMed]
- Andreyev, A.Y.; Kushnareva, Y.E.; Starkov, A.A. Mitochondrial metabolism of reactive oxygen species. Biochem. Biokhimiia 2005, 70, 200–214. [Google Scholar] [CrossRef]
- Azzu, V.; Brand, M.D. The on-off switches of the mitochondrial uncoupling proteins. Trends Biochem. Sci. 2010, 35, 298–307. [Google Scholar] [CrossRef] [Green Version]
- Hoffman, D.L.; Brookes, P.S. Oxygen sensitivity of mitochondrial reactive oxygen species generation depends on metabolic conditions. J. Biol. Chem. 2009, 284, 16236–16245. [Google Scholar] [CrossRef]
- Zhang, J.; Wang, Y.T.; Miller, J.H.; Day, M.M.; Munger, J.C.; Brookes, P.S. Accumulation of Succinate in Cardiac Ischemia Primarily Occurs via Canonical Krebs Cycle Activity. Cell Rep. 2018, 23, 2617–2628. [Google Scholar] [CrossRef] [Green Version]
- Chouchani, E.T.; Pell, V.R.; Gaude, E.; Aksentijevic, D.; Sundier, S.Y.; Robb, E.L.; Logan, A.; Nadtochiy, S.M.; Ord, E.N.J.; Smith, A.C.; et al. Ischaemic accumulation of succinate controls reperfusion injury through mitochondrial ROS. Nature 2014, 515, 431–435. [Google Scholar] [CrossRef] [Green Version]
- Scialo, F.; Sriram, A.; Fernandez-Ayala, D.; Gubina, N.; Lohmus, M.; Nelson, G.; Logan, A.; Cooper, H.M.; Navas, P.; Enriquez, J.A.; et al. Mitochondrial ROS Produced via Reverse Electron Transport Extend Animal Lifespan. Cell Metab. 2016, 23, 725–734. [Google Scholar] [CrossRef] [Green Version]
- Guaras, A.; Perales-Clemente, E.; Calvo, E.; Acin-Perez, R.; Loureiro-Lopez, M.; Pujol, C.; Martinez-Carrascoso, I.; Nunez, E.; Garcia-Marques, F.; Rodriguez-Hernandez, M.A.; et al. The CoQH2/CoQ Ratio Serves as a Sensor of Respiratory Chain Efficiency. Cell Rep. 2016, 15, 197–209. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Fernandez-Aguera, M.C.; Gao, L.; Gonzalez-Rodriguez, P.; Pintado, C.O.; Arias-Mayenco, I.; Garcia-Flores, P.; Garcia-Perganeda, A.; Pascual, A.; Ortega-Saenz, P.; Lopez-Barneo, J. Oxygen Sensing by Arterial Chemoreceptors Depends on Mitochondrial Complex I Signaling. Cell Metab. 2015, 22, 825–837. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Arias-Mayenco, I.; Gonzalez-Rodriguez, P.; Torres-Torrelo, H.; Gao, L.; Fernandez-Aguera, M.C.; Bonilla-Henao, V.; Ortega-Saenz, P.; Lopez-Barneo, J. Acute O2 Sensing: Role of Coenzyme QH2/Q Ratio and Mitochondrial ROS Compartmentalization. Cell Metab. 2018, 28, 145–158. [Google Scholar] [CrossRef] [PubMed]
- Lee, S.; Tak, E.; Lee, J.; Rashid, M.A.; Murphy, M.P.; Ha, J.; Kim, S.S. Mitochondrial H2O2 generated from electron transport chain complex I stimulates muscle differentiation. Cell Res. 2011, 21, 817–834. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Carroll, J.; Fearnley, I.M.; Skehel, J.M.; Shannon, R.J.; Hirst, J.; Walker, J.E. Bovine complex I is a complex of 45 different subunits. J. Biol. Chem. 2006, 281, 32724–32727. [Google Scholar] [CrossRef] [PubMed]
- Hirst, J. Mitochondrial complex I. Annu. Rev. Biochem. 2013, 82, 551–575. [Google Scholar] [CrossRef] [PubMed]
- Hirst, J. Towards the molecular mechanism of respiratory complex I. Biochem. J. 2009, 425, 327–339. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Wirth, C.; Brandt, U.; Hunte, C.; Zickermann, V. Structure and function of mitochondrial complex I. Biochim. Biophys. Acta 2016, 1857, 902–914. [Google Scholar] [CrossRef] [PubMed]
- Efremov, R.G.; Sazanov, L.A. Structure of the membrane domain of respiratory complex I. Nature 2011, 476, 414–420. [Google Scholar] [CrossRef]
- Drose, S.; Stepanova, A.; Galkin, A. Ischemic A/D transition of mitochondrial complex I and its role in ROS generation. Biochim. Biophys. Acta 2016, 1857, 946–957. [Google Scholar] [CrossRef] [Green Version]
- Genova, M.L.; Ventura, B.; Giuliano, G.; Bovina, C.; Formiggini, G.; Parenti Castelli, G.; Lenaz, G. The site of production of superoxide radical in mitochondrial Complex I is not a bound ubisemiquinone but presumably iron-sulfur cluster N2. FEBS Lett. 2001, 505, 364–368. [Google Scholar] [CrossRef]
- Kushnareva, Y.; Murphy, A.N.; Andreyev, A. Complex I-mediated reactive oxygen species generation: Modulation by cytochrome c and NAD(P)+ oxidation-reduction state. Biochem. J. 2002, 368, 545–553. [Google Scholar] [CrossRef] [PubMed]
- Liu, Y.; Fiskum, G.; Schubert, D. Generation of reactive oxygen species by the mitochondrial electron transport chain. J. Neurochem. 2002, 80, 780–787. [Google Scholar] [CrossRef] [PubMed]
- Turrens, J.F.; Boveris, A. Generation of superoxide anion by the NADH dehydrogenase of bovine heart mitochondria. Biochem. J. 1980, 191, 421–427. [Google Scholar] [CrossRef] [PubMed]
- Lambert, A.J.; Brand, M.D. Superoxide production by NADH:ubiquinone oxidoreductase (complex I) depends on the pH gradient across the mitochondrial inner membrane. Biochem. J. 2004, 382, 511–517. [Google Scholar] [CrossRef] [PubMed]
- Berry, B.J.; Trewin, A.J.; Amitrano, A.M.; Kim, M.; Wojtovich, A.P. Use the Protonmotive Force: Mitochondrial Uncoupling and Reactive Oxygen Species. J. Mol. Biol. 2018, 430, 3873–3891. [Google Scholar] [CrossRef] [PubMed]
- Votyakova, T.V.; Reynolds, I.J. DeltaPsi(m)-Dependent and -independent production of reactive oxygen species by rat brain mitochondria. J. Neurochem. 2001, 79, 266–277. [Google Scholar] [CrossRef] [PubMed]
- Komlodi, T.; Geibl, F.F.; Sassani, M.; Ambrus, A.; Tretter, L. Membrane potential and delta pH dependency of reverse electron transport-associated hydrogen peroxide production in brain and heart mitochondria. J. Bioenerg. Biomembr. 2018, 50, 355–365. [Google Scholar] [CrossRef] [Green Version]
- Kussmaul, L.; Hirst, J. The mechanism of superoxide production by NADH:ubiquinone oxidoreductase (complex I) from bovine heart mitochondria. Proc. Natl. Acad. Sci. USA 2006, 103, 7607–7612. [Google Scholar] [CrossRef] [Green Version]
- Kudin, A.P.; Bimpong-Buta, N.Y.; Vielhaber, S.; Elger, C.E.; Kunz, W.S. Characterization of superoxide-producing sites in isolated brain mitochondria. J. Biol. Chem. 2004, 279, 4127–4135. [Google Scholar] [CrossRef]
- Chance, B. The interaction of energy and electron transfer reactions in mitochondria. II. General properties of adenosine triphosphate-linked oxidation of cytochrome and reduction of pyridine nucleotide. J. Biol. Chem. 1961, 236, 1544–1554. [Google Scholar] [PubMed]
- Chance, B.; Hollunger, G. The interaction of energy and electron transfer reactions in mitochondria. I. General properties and nature of the products of succinate-linked reduction of pyridine nucleotide. J. Biol. Chem. 1961, 236, 1534–1543. [Google Scholar] [PubMed]
- Stepanova, A.; Kahl, A.; Konrad, C.; Ten, V.; Starkov, A.S.; Galkin, A. Reverse electron transfer results in a loss of flavin from mitochondrial complex I: Potential mechanism for brain ischemia reperfusion injury. J. Cereb. Blood Flow Metab. Off. J. Int. Soc. Cereb. Blood Flow Metab. 2017, 37, 3649–3658. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Hirst, J.; King, M.S.; Pryde, K.R. The production of reactive oxygen species by complex I. Biochem. Soc. Trans. 2008, 36, 976–980. [Google Scholar] [CrossRef] [PubMed]
- Lambert, A.J.; Buckingham, J.A.; Boysen, H.M.; Brand, M.D. Diphenyleneiodonium acutely inhibits reactive oxygen species production by mitochondrial complex I during reverse, but not forward electron transport. Biochim. Biophys. Acta 2008, 1777, 397–403. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Shabalina, I.G.; Nedergaard, J. Mitochondrial (‘mild’) uncoupling and ROS production: Physiologically relevant or not? Biochem. Soc. Trans. 2011, 39, 1305–1309. [Google Scholar] [CrossRef] [PubMed]
- Pell, V.R.; Chouchani, E.T.; Frezza, C.; Murphy, M.P.; Krieg, T. Succinate metabolism: A new therapeutic target for myocardial reperfusion injury. Cardiovasc. Res. 2016, 111, 134–141. [Google Scholar] [CrossRef] [PubMed]
- Dikalov, S.I.; Harrison, D.G. Methods for detection of mitochondrial and cellular reactive oxygen species. Antioxid. Redox Signal. 2014, 20, 372–382. [Google Scholar] [CrossRef]
- Hardy, M.; Zielonka, J.; Karoui, H.; Sikora, A.; Michalski, R.; Podsiadly, R.; Lopez, M.; Vasquez-Vivar, J.; Kalyanaraman, B.; Ouari, O. Detection and Characterization of Reactive Oxygen and Nitrogen Species in Biological Systems by Monitoring Species-Specific Products. Antioxid. Redox Signal. 2018, 28, 1416–1432. [Google Scholar] [CrossRef]
- Michalski, R.; Michalowski, B.; Sikora, A.; Zielonka, J.; Kalyanaraman, B. On the use of fluorescence lifetime imaging and dihydroethidium to detect superoxide in intact animals and ex vivo tissues: A reassessment. Free Radic. Biol. Med. 2014, 67, 278–284. [Google Scholar] [CrossRef]
- Zielonka, J.; Hardy, M.; Kalyanaraman, B. HPLC study of oxidation products of hydroethidine in chemical and biological systems: Ramifications in superoxide measurements. Free Radic. Biol. Med. 2009, 46, 329–338. [Google Scholar] [CrossRef] [PubMed]
- Kalyanaraman, B.; Hardy, M.; Podsiadly, R.; Cheng, G.; Zielonka, J. Recent developments in detection of superoxide radical anion and hydrogen peroxide: Opportunities, challenges, and implications in redox signaling. Arch. Biochem. Biophys. 2017, 617, 38–47. [Google Scholar] [CrossRef] [PubMed]
- Zielonka, J.; Kalyanaraman, B. Hydroethidine- and MitoSOX-derived red fluorescence is not a reliable indicator of intracellular superoxide formation: Another inconvenient truth. Free Radic. Biol. Med. 2010, 48, 983–1001. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Barnett, M.E.; Baran, T.M.; Foster, T.H.; Wojtovich, A.P. Quantification of light-induced miniSOG superoxide production using the selective marker, 2-hydroxyethidium. Free Radic. Biol. Med. 2018, 116, 134–140. [Google Scholar] [CrossRef] [PubMed]
- Shchepinova, M.M.; Cairns, A.G.; Prime, T.A.; Logan, A.; James, A.M.; Hall, A.R.; Vidoni, S.; Arndt, S.; Caldwell, S.T.; Prag, H.A.; et al. MitoNeoD: A Mitochondria-Targeted Superoxide Probe. Cell Chem. Biol. 2017, 24, 1285–1298 e1212. [Google Scholar] [CrossRef]
- Ermakova, Y.G.; Bilan, D.S.; Matlashov, M.E.; Mishina, N.M.; Markvicheva, K.N.; Subach, O.M.; Subach, F.V.; Bogeski, I.; Hoth, M.; Enikolopov, G.; et al. Red fluorescent genetically encoded indicator for intracellular hydrogen peroxide. Nat. Commun. 2014, 5, 5222. [Google Scholar] [CrossRef]
- Cheng, W.Y.; Larson, J.M.; Samet, J.M. Monitoring intracellular oxidative events using dynamic spectral unmixing microscopy. Methods 2014, 66, 345–352. [Google Scholar] [CrossRef]
- Bertolotti, M.; Bestetti, S.; Garcia-Manteiga, J.M.; Medrano-Fernandez, I.; Dal Mas, A.; Malosio, M.L.; Sitia, R. Tyrosine kinase signal modulation: A matter of H2O2 membrane permeability? Antioxid. Redox Signal. 2013, 19, 1447–1451. [Google Scholar] [CrossRef]
- Markvicheva, K.N.; Bilan, D.S.; Mishina, N.M.; Gorokhovatsky, A.Y.; Vinokurov, L.M.; Lukyanov, S.; Belousov, V.V. A genetically encoded sensor for H2O2 with expanded dynamic range. Bioorg. Med. Chem. 2011, 19, 1079–1084. [Google Scholar] [CrossRef]
- Belousov, V.V.; Fradkov, A.F.; Lukyanov, K.A.; Staroverov, D.B.; Shakhbazov, K.S.; Terskikh, A.V.; Lukyanov, S. Genetically encoded fluorescent indicator for intracellular hydrogen peroxide. Nat. Methods 2006, 3, 281–286. [Google Scholar] [CrossRef]
- Bilan, D.S.; Belousov, V.V. HyPer Family Probes: State of the Art. Antioxid. Redox Signal. 2016, 24, 731–751. [Google Scholar] [CrossRef] [PubMed]
- Roma, L.P.; Deponte, M.; Riemer, J.; Morgan, B. Mechanisms and Applications of Redox-Sensitive Green Fluorescent Protein-Based Hydrogen Peroxide Probes. Antioxid. Redox Signal. 2018, 29, 552–568. [Google Scholar] [CrossRef] [PubMed]
- Fernandez-Ayala, D.J.; Sanz, A.; Vartiainen, S.; Kemppainen, K.K.; Babusiak, M.; Mustalahti, E.; Costa, R.; Tuomela, T.; Zeviani, M.; Chung, J.; et al. Expression of the Ciona intestinalis alternative oxidase (AOX) in Drosophila complements defects in mitochondrial oxidative phosphorylation. Cell Metab. 2009, 9, 449–460. [Google Scholar] [CrossRef] [PubMed]
- Hoefnagel, M.H.; Wiskich, J.T. Activation of the plant alternative oxidase by high reduction levels of the Q-pool and pyruvate. Arch. Biochem. Biophys. 1998, 355, 262–270. [Google Scholar] [CrossRef] [PubMed]
- de Vries, S.; Grivell, L.A. Purification and characterization of a rotenone-insensitive NADH:Q6 oxidoreductase from mitochondria of Saccharomyces cerevisiae. Eur. J. Biochem. 1988, 176, 377–384. [Google Scholar] [CrossRef] [PubMed]
- Szibor, M.; Dhandapani, P.K.; Dufour, E.; Holmstrom, K.M.; Zhuang, Y.; Salwig, I.; Wittig, I.; Heidler, J.; Gizatullina, Z.; Gainutdinov, T.; et al. Broad AOX expression in a genetically tractable mouse model does not disturb normal physiology. Dis. Models Mech. 2017, 10, 163–171. [Google Scholar] [CrossRef] [PubMed]
- Saari, S.; Andjelkovic, A.; Garcia, G.S.; Jacobs, H.T.; Oliveira, M.T. Expression of Ciona intestinalis AOX causes male reproductive defects in Drosophila melanogaster. BMC Dev. Biol. 2017, 17, 9. [Google Scholar] [CrossRef] [PubMed]
- Hoffman, D.L.; Salter, J.D.; Brookes, P.S. Response of mitochondrial reactive oxygen species generation to steady-state oxygen tension: Implications for hypoxic cell signaling. Am. J. Physiol. Heart Circ. Physiol. 2007, 292, H101–H108. [Google Scholar] [CrossRef] [PubMed]
- Kang, P.T.; Chen, C.L.; Lin, P.; Chilian, W.M.; Chen, Y.R. Impairment of pH gradient and membrane potential mediates redox dysfunction in the mitochondria of the post-ischemic heart. Basic Res. Cardiol. 2017, 112, 36. [Google Scholar] [CrossRef] [PubMed]
- Brand, M.D.; Goncalves, R.L.; Orr, A.L.; Vargas, L.; Gerencser, A.A.; Borch Jensen, M.; Wang, Y.T.; Melov, S.; Turk, C.N.; Matzen, J.T.; et al. Suppressors of Superoxide-H2O2 Production at Site IQ of Mitochondrial Complex I Protect against Stem Cell Hyperplasia and Ischemia-Reperfusion Injury. Cell Metab. 2016, 24, 582–592. [Google Scholar] [CrossRef] [PubMed]
- Kotlyar, A.B.; Vinogradov, A.D. Slow active/inactive transition of the mitochondrial NADH-ubiquinone reductase. Biochim. Biophys. Acta 1990, 1019, 151–158. [Google Scholar] [CrossRef]
- Babot, M.; Birch, A.; Labarbuta, P.; Galkin, A. Characterisation of the active/de-active transition of mitochondrial complex I. Biochim. Biophys. Acta 2014, 1837, 1083–1092. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Gorenkova, N.; Robinson, E.; Grieve, D.J.; Galkin, A. Conformational change of mitochondrial complex I increases ROS sensitivity during ischemia. Antioxid. Redox Signal. 2013, 19, 1459–1468. [Google Scholar] [CrossRef] [PubMed]
- Stepanova, A.; Konrad, C.; Guerrero-Castillo, S.; Manfredi, G.; Vannucci, S.; Arnold, S.; Galkin, A. Deactivation of mitochondrial complex I after hypoxia-ischemia in the immature brain. J. Cereb. Blood Flow Metab. Off. J. Int. Soc. Cereb. Blood Flow Metab. 2018. [Google Scholar] [CrossRef] [PubMed]
- Treberg, J.R.; Quinlan, C.L.; Brand, M.D. Evidence for two sites of superoxide production by mitochondrial NADH-ubiquinone oxidoreductase (complex I). J. Biol. Chem. 2011, 286, 27103–27110. [Google Scholar] [CrossRef] [PubMed]
- Orr, A.L.; Ashok, D.; Sarantos, M.R.; Shi, T.; Hughes, R.E.; Brand, M.D. Inhibitors of ROS production by the ubiquinone-binding site of mitochondrial complex I identified by chemical screening. Free Radic. Biol. Med. 2013, 65, 1047–1059. [Google Scholar] [CrossRef] [Green Version]
- Detaille, D.; Pasdois, P.; Semont, A.; Dos Santos, P.; Diolez, P. An old medicine as a new drug to prevent mitochondrial complex I from producing oxygen radicals. PLoS ONE 2019, 14, e0216385. [Google Scholar] [CrossRef]
- Mohsin, A.A.; Chen, Q.; Quan, N.; Rousselle, T.; Maceyka, M.W.; Samidurai, A.; Thompson, J.; Hu, Y.; Li, J.; Lesnefsky, E.J. Mitochondrial Complex I Inhibition by Metformin Limits Reperfusion Injury. J. Pharmacol. Exp. Ther. 2019, 369, 282–290. [Google Scholar] [CrossRef]
- Xie, D.; Hou, F.F.; Fu, B.L.; Zhang, X.; Liang, M. High level of proteinuria during treatment with renin-angiotensin inhibitors is a strong predictor of renal outcome in nondiabetic kidney disease. J. Clin. Pharmacol. 2011, 51, 1025–1034. [Google Scholar] [CrossRef]
- Steinhubl, S.R. Why have antioxidants failed in clinical trials? Am. J. Cardiol. 2008, 101, S14–S19. [Google Scholar] [CrossRef]
- Shuaib, A.; Lees, K.R.; Lyden, P.; Grotta, J.; Davalos, A.; Davis, S.M.; Diener, H.C.; Ashwood, T.; Wasiewski, W.W.; Emeribe, U.; et al. NXY-059 for the treatment of acute ischemic stroke. N. Engl. J. Med. 2007, 357, 562–571. [Google Scholar] [CrossRef] [PubMed]
- Ganote, C.E.; Armstrong, S.C. Effects of CCCP-induced mitochondrial uncoupling and cyclosporin A on cell volume, cell injury and preconditioning protection of isolated rabbit cardiomyocytes. J. Mol. Cell. Cardiol. 2003, 35, 749–759. [Google Scholar] [CrossRef]
- Brennan, J.P.; Berry, R.G.; Baghai, M.; Duchen, M.R.; Shattock, M.J. FCCP is cardioprotective at concentrations that cause mitochondrial oxidation without detectable depolarisation. Cardiovasc. Res. 2006, 72, 322–330. [Google Scholar] [CrossRef] [PubMed]
- Geisler, J.G.; Marosi, K.; Halpern, J.; Mattson, M.P. DNP, mitochondrial uncoupling, and neuroprotection: A little dab’ll do ya. Alzheimer’s Dement. J. Alzheimer’s Assoc. 2017, 13, 582–591. [Google Scholar] [CrossRef] [PubMed]
- Lopez-Barneo, J.; Ortega-Saenz, P.; Gonzalez-Rodriguez, P.; Fernandez-Aguera, M.C.; Macias, D.; Pardal, R.; Gao, L. Oxygen-sensing by arterial chemoreceptors: Mechanisms and medical translation. Mol. Asp. Med. 2016, 47–48, 90–108. [Google Scholar] [CrossRef]
- Salvati, K.A.; Beenhakker, M.P. Out of thin air: Hyperventilation-triggered seizures. Brain Res. 2019, 1703, 41–52. [Google Scholar] [CrossRef]
- Wyatt, C.N.; Buckler, K.J. The effect of mitochondrial inhibitors on membrane currents in isolated neonatal rat carotid body type I cells. J. Physiol. 2004, 556, 175–191. [Google Scholar] [CrossRef]
- McElroy, G.S.; Chandel, N.S. Mitochondria control acute and chronic responses to hypoxia. Exp. Cell Res. 2017, 356, 217–222. [Google Scholar] [CrossRef]
- Dunham-Snary, K.J.; Wu, D.; Potus, F.; Sykes, E.A.; Mewburn, J.D.; Charles, R.L.; Eaton, P.; Sultanian, R.A.; Archer, S.L. Ndufs2, a Core Subunit of Mitochondrial Complex I, Is Essential for Acute Oxygen-Sensing and Hypoxic Pulmonary Vasoconstriction. Circ. Res. 2019, 124, 1727–1746. [Google Scholar] [CrossRef]
- Yoo, S.Z.; No, M.H.; Heo, J.W.; Park, D.H.; Kang, J.H.; Kim, J.H.; Seo, D.Y.; Han, J.; Jung, S.J.; Kwak, H.B. Effects of Acute Exercise on Mitochondrial Function, Dynamics, and Mitophagy in Rat Cardiac and Skeletal Muscles. Int. Neurourol. J. 2019, 23, S22–S31. [Google Scholar] [CrossRef]
- Xie, K.; Ngo, S.; Rong, J.; Sheppard, A. Modulation of mitochondrial respiration underpins neuronal differentiation enhanced by lutein. Neural Regen. Res. 2019, 14, 87–99. [Google Scholar] [CrossRef] [PubMed]
- Sanz, A.; Soikkeli, M.; Portero-Otin, M.; Wilson, A.; Kemppainen, E.; McIlroy, G.; Ellila, S.; Kemppainen, K.K.; Tuomela, T.; Lakanmaa, M.; et al. Expression of the yeast NADH dehydrogenase Ndi1 in Drosophila confers increased lifespan independently of dietary restriction. Proc. Natl. Acad. Sci. USA 2010, 107, 9105–9110. [Google Scholar] [CrossRef]
- Bahadorani, S.; Cho, J.; Lo, T.; Contreras, H.; Lawal, H.O.; Krantz, D.E.; Bradley, T.J.; Walker, D.W. Neuronal expression of a single-subunit yeast NADH-ubiquinone oxidoreductase (Ndi1) extends Drosophila lifespan. Aging Cell 2010, 9, 191–202. [Google Scholar] [CrossRef] [PubMed]
- DeCorby, A.; Gaskova, D.; Sayles, L.C.; Lemire, B.D. Expression of Ndi1p, an alternative NADH:ubiquinone oxidoreductase, increases mitochondrial membrane potential in a C. elegans model of mitochondrial disease. Biochim. Biophys. Acta 2007, 1767, 1157–1163. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Cossard, R.; Esposito, M.; Sellem, C.H.; Pitayu, L.; Vasnier, C.; Delahodde, A.; Dassa, E.P. Caenorhabditis elegans expressing the Saccharomyces cerevisiae NADH alternative dehydrogenase Ndi1p, as a tool to identify new genes involved in complex I related diseases. Front. Genet. 2015, 6, 206. [Google Scholar] [CrossRef] [PubMed]
- Acin-Perez, R.; Enriquez, J.A. The function of the respiratory supercomplexes: The plasticity model. Biochim. Biophys. Acta 2014, 1837, 444–450. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Lapuente-Brun, E.; Moreno-Loshuertos, R.; Acin-Perez, R.; Latorre-Pellicer, A.; Colas, C.; Balsa, E.; Perales-Clemente, E.; Quiros, P.M.; Calvo, E.; Rodriguez-Hernandez, M.A.; et al. Supercomplex assembly determines electron flux in the mitochondrial electron transport chain. Science 2013, 340, 1567–1570. [Google Scholar] [CrossRef]
- Jones, D.P.; Sies, H. The Redox Code. Antioxid. Redox Signal. 2015, 23, 734–746. [Google Scholar] [CrossRef] [Green Version]
- Trewin, A.J.; Bahr, L.L.; Almast, A.; Berry, B.J.; Wei, A.Y.; Foster, T.H.; Wojtovich, A.P. Mitochondrial Reactive Oxygen Species Generated at the Complex-II Matrix or Intermembrane Space Microdomain Have Distinct Effects on Redox Signaling and Stress Sensitivity in Caenorhabditis elegans. Antioxid. Redox Signal. 2019, 31, 594–607. [Google Scholar] [CrossRef]
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Onukwufor, J.O.; Berry, B.J.; Wojtovich, A.P. Physiologic Implications of Reactive Oxygen Species Production by Mitochondrial Complex I Reverse Electron Transport. Antioxidants 2019, 8, 285. https://doi.org/10.3390/antiox8080285
Onukwufor JO, Berry BJ, Wojtovich AP. Physiologic Implications of Reactive Oxygen Species Production by Mitochondrial Complex I Reverse Electron Transport. Antioxidants. 2019; 8(8):285. https://doi.org/10.3390/antiox8080285
Chicago/Turabian StyleOnukwufor, John O., Brandon J. Berry, and Andrew P. Wojtovich. 2019. "Physiologic Implications of Reactive Oxygen Species Production by Mitochondrial Complex I Reverse Electron Transport" Antioxidants 8, no. 8: 285. https://doi.org/10.3390/antiox8080285
APA StyleOnukwufor, J. O., Berry, B. J., & Wojtovich, A. P. (2019). Physiologic Implications of Reactive Oxygen Species Production by Mitochondrial Complex I Reverse Electron Transport. Antioxidants, 8(8), 285. https://doi.org/10.3390/antiox8080285