Effect of F16-Betulin Conjugate on Mitochondrial Membranes and Its Role in Cell Death Initiation
This work demonstrates the effects of a newly synthesized conjugate of the plant triterpenoid betulin and the penetrating cation F16 used for mitochondrial targeting. The resulting F16-betulin conjugate revealed a mitochondria-targeted effect, decreasing the mitochondrial potential and inducing supe...
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| Format: | Article |
| Language: | English |
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MDPI AG
2021-05-01
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| Series: | Membranes |
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| Online Access: | https://www.mdpi.com/2077-0375/11/5/352 |
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| author | Mikhail V. Dubinin Alena A. Semenova Darya A. Nedopekina Eldar V. Davletshin Anna Yu. Spivak Konstantin N. Belosludtsev |
| author_facet | Mikhail V. Dubinin Alena A. Semenova Darya A. Nedopekina Eldar V. Davletshin Anna Yu. Spivak Konstantin N. Belosludtsev |
| author_sort | Mikhail V. Dubinin |
| collection | DOAJ |
| description | This work demonstrates the effects of a newly synthesized conjugate of the plant triterpenoid betulin and the penetrating cation F16 used for mitochondrial targeting. The resulting F16-betulin conjugate revealed a mitochondria-targeted effect, decreasing the mitochondrial potential and inducing superoxide overproduction in rat thymocytes <i>in vitro</i>. It has been suggested that this may cause the cytotoxic effect of the conjugate, which significantly exceeds the effectiveness of its precursors, betulin and F16. Using isolated rat liver mitochondria, we found that the F16-betulin conjugate has a surface-active effect on mitochondrial membranes, causing organelle aggregation. This effect of the derivative resulted in a dose-dependent decrease in mitochondrial transmembrane potential, as well as suppression of respiration and oxidative phosphorylation, especially in the case of nicotinamide adenine dinucleotide (NAD)-fueled organelles. In addition, the F16-betulin conjugate caused an increase in H<sub>2</sub>O<sub>2</sub> generation by mitochondria fueled with glutamate and malate. These effects of the derivative can presumably be due to the powerful suppression of the redox activity of complex I of the mitochondrial electron transport chain. The paper discusses how the mitochondria-targeted effects of the F16-betulin conjugate may be related to its cytotoxic effects. |
| first_indexed | 2024-03-10T11:33:47Z |
| format | Article |
| id | doaj.art-858a1a5832f24a6fb636b50da2395e68 |
| institution | Directory Open Access Journal |
| issn | 2077-0375 |
| language | English |
| last_indexed | 2024-03-10T11:33:47Z |
| publishDate | 2021-05-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Membranes |
| spelling | doaj.art-858a1a5832f24a6fb636b50da2395e682023-11-21T19:02:23ZengMDPI AGMembranes2077-03752021-05-0111535210.3390/membranes11050352Effect of F16-Betulin Conjugate on Mitochondrial Membranes and Its Role in Cell Death InitiationMikhail V. Dubinin0Alena A. Semenova1Darya A. Nedopekina2Eldar V. Davletshin3Anna Yu. Spivak4Konstantin N. Belosludtsev5Department of Biochemistry, Cell Biology and Microbiology, Mari State University, pl. Lenina 1, 424001 Yoshkar-Ola, RussiaDepartment of Biochemistry, Cell Biology and Microbiology, Mari State University, pl. Lenina 1, 424001 Yoshkar-Ola, RussiaInstitute of Petrochemistry and Catalysis, Russian Academy of Sciences, Prospekt Oktyabrya 141, 450075 Ufa, RussiaInstitute of Petrochemistry and Catalysis, Russian Academy of Sciences, Prospekt Oktyabrya 141, 450075 Ufa, RussiaInstitute of Petrochemistry and Catalysis, Russian Academy of Sciences, Prospekt Oktyabrya 141, 450075 Ufa, RussiaDepartment of Biochemistry, Cell Biology and Microbiology, Mari State University, pl. Lenina 1, 424001 Yoshkar-Ola, RussiaThis work demonstrates the effects of a newly synthesized conjugate of the plant triterpenoid betulin and the penetrating cation F16 used for mitochondrial targeting. The resulting F16-betulin conjugate revealed a mitochondria-targeted effect, decreasing the mitochondrial potential and inducing superoxide overproduction in rat thymocytes <i>in vitro</i>. It has been suggested that this may cause the cytotoxic effect of the conjugate, which significantly exceeds the effectiveness of its precursors, betulin and F16. Using isolated rat liver mitochondria, we found that the F16-betulin conjugate has a surface-active effect on mitochondrial membranes, causing organelle aggregation. This effect of the derivative resulted in a dose-dependent decrease in mitochondrial transmembrane potential, as well as suppression of respiration and oxidative phosphorylation, especially in the case of nicotinamide adenine dinucleotide (NAD)-fueled organelles. In addition, the F16-betulin conjugate caused an increase in H<sub>2</sub>O<sub>2</sub> generation by mitochondria fueled with glutamate and malate. These effects of the derivative can presumably be due to the powerful suppression of the redox activity of complex I of the mitochondrial electron transport chain. The paper discusses how the mitochondria-targeted effects of the F16-betulin conjugate may be related to its cytotoxic effects.https://www.mdpi.com/2077-0375/11/5/352F16betulinthymocytesmitochondriaoxidative phosphorylationROS |
| spellingShingle | Mikhail V. Dubinin Alena A. Semenova Darya A. Nedopekina Eldar V. Davletshin Anna Yu. Spivak Konstantin N. Belosludtsev Effect of F16-Betulin Conjugate on Mitochondrial Membranes and Its Role in Cell Death Initiation Membranes F16 betulin thymocytes mitochondria oxidative phosphorylation ROS |
| title | Effect of F16-Betulin Conjugate on Mitochondrial Membranes and Its Role in Cell Death Initiation |
| title_full | Effect of F16-Betulin Conjugate on Mitochondrial Membranes and Its Role in Cell Death Initiation |
| title_fullStr | Effect of F16-Betulin Conjugate on Mitochondrial Membranes and Its Role in Cell Death Initiation |
| title_full_unstemmed | Effect of F16-Betulin Conjugate on Mitochondrial Membranes and Its Role in Cell Death Initiation |
| title_short | Effect of F16-Betulin Conjugate on Mitochondrial Membranes and Its Role in Cell Death Initiation |
| title_sort | effect of f16 betulin conjugate on mitochondrial membranes and its role in cell death initiation |
| topic | F16 betulin thymocytes mitochondria oxidative phosphorylation ROS |
| url | https://www.mdpi.com/2077-0375/11/5/352 |
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