Mathematical Modeling of ROS Production and Diode-like Behavior in the SDHA/SDHB Subcomplex of Succinate Dehydrogenases in Reverse Quinol-Fumarate Reductase Direction
Succinate dehydrogenase (SDH) plays an important role in reverse electron transfer during hypoxia/anoxia, in particular, in ischemia, when blood supply to an organ is disrupted, and oxygen is not available. It was detected in the voltammetry studies about three decades ago that the SDHA/SDHB subcomp...
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| Format: | Article |
| Language: | English |
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MDPI AG
2022-12-01
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| Series: | International Journal of Molecular Sciences |
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| Online Access: | https://www.mdpi.com/1422-0067/23/24/15596 |
| _version_ | 1797457310308630528 |
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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 | Succinate dehydrogenase (SDH) plays an important role in reverse electron transfer during hypoxia/anoxia, in particular, in ischemia, when blood supply to an organ is disrupted, and oxygen is not available. It was detected in the voltammetry studies about three decades ago that the SDHA/SDHB subcomplex of SDH can have such a strong nonlinear property as a “tunnel-diode” behavior in reverse quinol-fumarate reductase direction. The molecular and kinetic mechanisms of this phenomenon, that is, a strong drop in the rate of fumarate reduction as the driving force is increased, are still unclear. In order to account for this property of SDH, we developed and analyzed a mechanistic computational model of reverse electron transfer in the SDHA/SDHB subcomplex of SDH. It was shown that a decrease in the rate of succinate release from the active center during fumarate reduction quantitatively explains the experimentally observed tunnel-diode behavior in SDH and threshold values of the electrode potential of about −80 mV. Computational analysis of ROS production in the SDHA/SDHB subcomplex of SDH during reverse electron transfer predicts that the rate of ROS production decreases when the tunnel-diode behavior appears. These results predict a low rate of ROS production by the SDHA/SDHB subcomplex of SDH during ischemia. |
| first_indexed | 2024-03-09T16:19:26Z |
| format | Article |
| id | doaj.art-1bab4d5e026747929bdba15f14a2dbe2 |
| institution | Directory Open Access Journal |
| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-03-09T16:19:26Z |
| publishDate | 2022-12-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | International Journal of Molecular Sciences |
| spelling | doaj.art-1bab4d5e026747929bdba15f14a2dbe22023-11-24T15:24:20ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672022-12-0123241559610.3390/ijms232415596Mathematical Modeling of ROS Production and Diode-like Behavior in the SDHA/SDHB Subcomplex of Succinate Dehydrogenases in Reverse Quinol-Fumarate Reductase DirectionNikolay I. Markevich0Lubov N. Markevich1Institute of Theoretical and Experimental Biophysics of RAS, 142290 Pushchino, RussiaInstitute of Cell Biophysics of RAS, 142290 Pushchino, RussiaSuccinate dehydrogenase (SDH) plays an important role in reverse electron transfer during hypoxia/anoxia, in particular, in ischemia, when blood supply to an organ is disrupted, and oxygen is not available. It was detected in the voltammetry studies about three decades ago that the SDHA/SDHB subcomplex of SDH can have such a strong nonlinear property as a “tunnel-diode” behavior in reverse quinol-fumarate reductase direction. The molecular and kinetic mechanisms of this phenomenon, that is, a strong drop in the rate of fumarate reduction as the driving force is increased, are still unclear. In order to account for this property of SDH, we developed and analyzed a mechanistic computational model of reverse electron transfer in the SDHA/SDHB subcomplex of SDH. It was shown that a decrease in the rate of succinate release from the active center during fumarate reduction quantitatively explains the experimentally observed tunnel-diode behavior in SDH and threshold values of the electrode potential of about −80 mV. Computational analysis of ROS production in the SDHA/SDHB subcomplex of SDH during reverse electron transfer predicts that the rate of ROS production decreases when the tunnel-diode behavior appears. These results predict a low rate of ROS production by the SDHA/SDHB subcomplex of SDH during ischemia.https://www.mdpi.com/1422-0067/23/24/15596succinate dehydrogenase (SDH)a tunnel-diode behaviourfumarate reductioncomplex IIreactive oxygen species (ROS)computational model |
| spellingShingle | Nikolay I. Markevich Lubov N. Markevich Mathematical Modeling of ROS Production and Diode-like Behavior in the SDHA/SDHB Subcomplex of Succinate Dehydrogenases in Reverse Quinol-Fumarate Reductase Direction International Journal of Molecular Sciences succinate dehydrogenase (SDH) a tunnel-diode behaviour fumarate reduction complex II reactive oxygen species (ROS) computational model |
| title | Mathematical Modeling of ROS Production and Diode-like Behavior in the SDHA/SDHB Subcomplex of Succinate Dehydrogenases in Reverse Quinol-Fumarate Reductase Direction |
| title_full | Mathematical Modeling of ROS Production and Diode-like Behavior in the SDHA/SDHB Subcomplex of Succinate Dehydrogenases in Reverse Quinol-Fumarate Reductase Direction |
| title_fullStr | Mathematical Modeling of ROS Production and Diode-like Behavior in the SDHA/SDHB Subcomplex of Succinate Dehydrogenases in Reverse Quinol-Fumarate Reductase Direction |
| title_full_unstemmed | Mathematical Modeling of ROS Production and Diode-like Behavior in the SDHA/SDHB Subcomplex of Succinate Dehydrogenases in Reverse Quinol-Fumarate Reductase Direction |
| title_short | Mathematical Modeling of ROS Production and Diode-like Behavior in the SDHA/SDHB Subcomplex of Succinate Dehydrogenases in Reverse Quinol-Fumarate Reductase Direction |
| title_sort | mathematical modeling of ros production and diode like behavior in the sdha sdhb subcomplex of succinate dehydrogenases in reverse quinol fumarate reductase direction |
| topic | succinate dehydrogenase (SDH) a tunnel-diode behaviour fumarate reduction complex II reactive oxygen species (ROS) computational model |
| url | https://www.mdpi.com/1422-0067/23/24/15596 |
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