Computational Modeling Analysis of Kinetics of Fumarate Reductase Activity and ROS Production during Reverse Electron Transfer in Mitochondrial Respiratory Complex II
Reverse electron transfer in mitochondrial complex II (CII) plays an important role in hypoxia/anoxia, in particular, in ischemia, when the blood supply to an organ is disrupted and oxygen is not available. A computational model of CII was developed in this work to facilitate the quantitative analys...
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| Language: | English |
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MDPI AG
2023-05-01
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| Series: | International Journal of Molecular Sciences |
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| Online Access: | https://www.mdpi.com/1422-0067/24/9/8291 |
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| author | Nikolay I. Markevich Lubov N. Markevich |
| author_facet | Nikolay I. Markevich Lubov N. Markevich |
| author_sort | Nikolay I. Markevich |
| collection | DOAJ |
| description | Reverse electron transfer in mitochondrial complex II (CII) plays an important role in hypoxia/anoxia, in particular, in ischemia, when the blood supply to an organ is disrupted and oxygen is not available. A computational model of CII was developed in this work to facilitate the quantitative analysis of the kinetics of quinol-fumarate reduction as well as ROS production during reverse electron transfer in CII. The model consists of 20 ordinary differential equations and 7 moiety conservation equations. The parameter values were determined at which the kinetics of electron transfer in CII in both forward and reverse directions would be explained simultaneously. The possibility of the existence of the “tunnel diode” behavior in the reverse electron transfer in CII, where the driving force is QH<sub>2</sub>, was tested. It was found that any high concentrations of QH<sub>2</sub> and fumarate are insufficient for the appearance of a tunnel effect. The results of computer modeling show that the maximum rate of succinate production cannot provide a high concentration of succinate in ischemia. Furthermore, computational modeling results predict a very low rate of ROS production, about 50 pmol/min/mg mitochondrial protein, which is considerably less than 1000 pmol/min/mg protein observed in CII in forward direction. |
| first_indexed | 2024-03-11T04:16:38Z |
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| id | doaj.art-e8384f13a6a947598ef2518d2a0e7588 |
| institution | Directory Open Access Journal |
| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-03-11T04:16:38Z |
| publishDate | 2023-05-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | International Journal of Molecular Sciences |
| spelling | doaj.art-e8384f13a6a947598ef2518d2a0e75882023-11-17T23:07:35ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672023-05-01249829110.3390/ijms24098291Computational Modeling Analysis of Kinetics of Fumarate Reductase Activity and ROS Production during Reverse Electron Transfer in Mitochondrial Respiratory Complex IINikolay I. Markevich0Lubov N. Markevich1Institute of Theoretical and Experimental Biophysics of RAS, Pushchino, Moscow 142290, RussiaInstitute of Cell Biophysics of RAS, Pushchino, Moscow 142290, RussiaReverse electron transfer in mitochondrial complex II (CII) plays an important role in hypoxia/anoxia, in particular, in ischemia, when the blood supply to an organ is disrupted and oxygen is not available. A computational model of CII was developed in this work to facilitate the quantitative analysis of the kinetics of quinol-fumarate reduction as well as ROS production during reverse electron transfer in CII. The model consists of 20 ordinary differential equations and 7 moiety conservation equations. The parameter values were determined at which the kinetics of electron transfer in CII in both forward and reverse directions would be explained simultaneously. The possibility of the existence of the “tunnel diode” behavior in the reverse electron transfer in CII, where the driving force is QH<sub>2</sub>, was tested. It was found that any high concentrations of QH<sub>2</sub> and fumarate are insufficient for the appearance of a tunnel effect. The results of computer modeling show that the maximum rate of succinate production cannot provide a high concentration of succinate in ischemia. Furthermore, computational modeling results predict a very low rate of ROS production, about 50 pmol/min/mg mitochondrial protein, which is considerably less than 1000 pmol/min/mg protein observed in CII in forward direction.https://www.mdpi.com/1422-0067/24/9/8291succinate dehydrogenase (SDH)a tunnel diode behaviorfumarate reductioncomplex IIreactive oxygen species (ROS)computational model |
| spellingShingle | Nikolay I. Markevich Lubov N. Markevich Computational Modeling Analysis of Kinetics of Fumarate Reductase Activity and ROS Production during Reverse Electron Transfer in Mitochondrial Respiratory Complex II International Journal of Molecular Sciences succinate dehydrogenase (SDH) a tunnel diode behavior fumarate reduction complex II reactive oxygen species (ROS) computational model |
| title | Computational Modeling Analysis of Kinetics of Fumarate Reductase Activity and ROS Production during Reverse Electron Transfer in Mitochondrial Respiratory Complex II |
| title_full | Computational Modeling Analysis of Kinetics of Fumarate Reductase Activity and ROS Production during Reverse Electron Transfer in Mitochondrial Respiratory Complex II |
| title_fullStr | Computational Modeling Analysis of Kinetics of Fumarate Reductase Activity and ROS Production during Reverse Electron Transfer in Mitochondrial Respiratory Complex II |
| title_full_unstemmed | Computational Modeling Analysis of Kinetics of Fumarate Reductase Activity and ROS Production during Reverse Electron Transfer in Mitochondrial Respiratory Complex II |
| title_short | Computational Modeling Analysis of Kinetics of Fumarate Reductase Activity and ROS Production during Reverse Electron Transfer in Mitochondrial Respiratory Complex II |
| title_sort | computational modeling analysis of kinetics of fumarate reductase activity and ros production during reverse electron transfer in mitochondrial respiratory complex ii |
| topic | succinate dehydrogenase (SDH) a tunnel diode behavior fumarate reduction complex II reactive oxygen species (ROS) computational model |
| url | https://www.mdpi.com/1422-0067/24/9/8291 |
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