Different Sensitivity of Control and MICU1- and MICU2-Ablated <i>Trypanosoma cruzi</i> Mitochondrial Calcium Uniporter Complex to Ruthenium-Based Inhibitors
The mitochondrial Ca<sup>2+</sup> uptake in trypanosomatids shares biochemical characteristics with that of animals. However, the composition of the mitochondrial Ca<sup>2+</sup> uniporter complex (MCUC) in these parasites is quite peculiar, suggesting lineage-specific adapta...
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| Format: | Article |
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MDPI AG
2020-12-01
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| Series: | International Journal of Molecular Sciences |
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| Online Access: | https://www.mdpi.com/1422-0067/21/23/9316 |
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| author | Mayara S. Bertolini Roberto Docampo |
| author_facet | Mayara S. Bertolini Roberto Docampo |
| author_sort | Mayara S. Bertolini |
| collection | DOAJ |
| description | The mitochondrial Ca<sup>2+</sup> uptake in trypanosomatids shares biochemical characteristics with that of animals. However, the composition of the mitochondrial Ca<sup>2+</sup> uniporter complex (MCUC) in these parasites is quite peculiar, suggesting lineage-specific adaptations. In this work, we compared the inhibitory activity of ruthenium red (RuRed) and Ru360, the most commonly used MCUC inhibitors, with that of the recently described inhibitor Ru265, on <i>Trypanosoma cruzi</i>, the agent of Chagas disease. Ru265 was more potent than Ru360 and RuRed in inhibiting mitochondrial Ca<sup>2+</sup> transport in permeabilized cells. When dose-response effects were investigated, an increase in sensitivity for Ru360 and Ru265 was observed in <i>TcMICU1</i>-KO and <i>TcMICU2</i>-KO cells as compared with control cells. In the presence of RuRed, a significant increase in sensitivity was observed only in <i>TcMICU2</i>-KO cells. However, application of Ru265 to intact cells did not affect growth and respiration of epimastigotes, mitochondrial Ca<sup>2+</sup> uptake in Rhod-2-labeled intact cells, or attachment to host cells and infection by trypomastigotes, suggesting a low permeability for this compound in trypanosomes. |
| first_indexed | 2024-03-10T14:17:06Z |
| format | Article |
| id | doaj.art-fd662f99df4249a999b310bca98e5510 |
| institution | Directory Open Access Journal |
| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-03-10T14:17:06Z |
| publishDate | 2020-12-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | International Journal of Molecular Sciences |
| spelling | doaj.art-fd662f99df4249a999b310bca98e55102023-11-20T23:44:18ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672020-12-012123931610.3390/ijms21239316Different Sensitivity of Control and MICU1- and MICU2-Ablated <i>Trypanosoma cruzi</i> Mitochondrial Calcium Uniporter Complex to Ruthenium-Based InhibitorsMayara S. Bertolini0Roberto Docampo1Center for Tropical and Emerging Global Diseases and Department of Cellular Biology, University of Georgia, Athens, GA 30606, USACenter for Tropical and Emerging Global Diseases and Department of Cellular Biology, University of Georgia, Athens, GA 30606, USAThe mitochondrial Ca<sup>2+</sup> uptake in trypanosomatids shares biochemical characteristics with that of animals. However, the composition of the mitochondrial Ca<sup>2+</sup> uniporter complex (MCUC) in these parasites is quite peculiar, suggesting lineage-specific adaptations. In this work, we compared the inhibitory activity of ruthenium red (RuRed) and Ru360, the most commonly used MCUC inhibitors, with that of the recently described inhibitor Ru265, on <i>Trypanosoma cruzi</i>, the agent of Chagas disease. Ru265 was more potent than Ru360 and RuRed in inhibiting mitochondrial Ca<sup>2+</sup> transport in permeabilized cells. When dose-response effects were investigated, an increase in sensitivity for Ru360 and Ru265 was observed in <i>TcMICU1</i>-KO and <i>TcMICU2</i>-KO cells as compared with control cells. In the presence of RuRed, a significant increase in sensitivity was observed only in <i>TcMICU2</i>-KO cells. However, application of Ru265 to intact cells did not affect growth and respiration of epimastigotes, mitochondrial Ca<sup>2+</sup> uptake in Rhod-2-labeled intact cells, or attachment to host cells and infection by trypomastigotes, suggesting a low permeability for this compound in trypanosomes.https://www.mdpi.com/1422-0067/21/23/9316calciummitochondrial calcium uniporterruthenium red<i>Trypanosoma cruzi</i> |
| spellingShingle | Mayara S. Bertolini Roberto Docampo Different Sensitivity of Control and MICU1- and MICU2-Ablated <i>Trypanosoma cruzi</i> Mitochondrial Calcium Uniporter Complex to Ruthenium-Based Inhibitors International Journal of Molecular Sciences calcium mitochondrial calcium uniporter ruthenium red <i>Trypanosoma cruzi</i> |
| title | Different Sensitivity of Control and MICU1- and MICU2-Ablated <i>Trypanosoma cruzi</i> Mitochondrial Calcium Uniporter Complex to Ruthenium-Based Inhibitors |
| title_full | Different Sensitivity of Control and MICU1- and MICU2-Ablated <i>Trypanosoma cruzi</i> Mitochondrial Calcium Uniporter Complex to Ruthenium-Based Inhibitors |
| title_fullStr | Different Sensitivity of Control and MICU1- and MICU2-Ablated <i>Trypanosoma cruzi</i> Mitochondrial Calcium Uniporter Complex to Ruthenium-Based Inhibitors |
| title_full_unstemmed | Different Sensitivity of Control and MICU1- and MICU2-Ablated <i>Trypanosoma cruzi</i> Mitochondrial Calcium Uniporter Complex to Ruthenium-Based Inhibitors |
| title_short | Different Sensitivity of Control and MICU1- and MICU2-Ablated <i>Trypanosoma cruzi</i> Mitochondrial Calcium Uniporter Complex to Ruthenium-Based Inhibitors |
| title_sort | different sensitivity of control and micu1 and micu2 ablated i trypanosoma cruzi i mitochondrial calcium uniporter complex to ruthenium based inhibitors |
| topic | calcium mitochondrial calcium uniporter ruthenium red <i>Trypanosoma cruzi</i> |
| url | https://www.mdpi.com/1422-0067/21/23/9316 |
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