Citrate Regulates the <i>Saccharomyces cerevisiae</i> Mitochondrial GDP/GTP Carrier (Ggc1p) by Triggering Unidirectional Transport of GTP
The yeast mitochondrial transport of GTP and GDP is mediated by Ggc1p, a member of the mitochondrial carrier family. The physiological role of Ggc1p in <i>S. cerevisiae</i> is probably to transport GTP into mitochondria in exchange for GDP generated in the matrix. <i>ggc1</i>...
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MDPI AG
2022-07-01
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| Series: | Journal of Fungi |
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| Online Access: | https://www.mdpi.com/2309-608X/8/8/795 |
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| author | Roberta Seccia Silvia De Santis Maria A. Di Noia Ferdinando Palmieri Daniela V. Miniero Raffaele Marmo Eleonora Paradies Antonella Santoro Ciro L. Pierri Luigi Palmieri Carlo M. T. Marobbio Angelo Vozza |
| author_facet | Roberta Seccia Silvia De Santis Maria A. Di Noia Ferdinando Palmieri Daniela V. Miniero Raffaele Marmo Eleonora Paradies Antonella Santoro Ciro L. Pierri Luigi Palmieri Carlo M. T. Marobbio Angelo Vozza |
| author_sort | Roberta Seccia |
| collection | DOAJ |
| description | The yeast mitochondrial transport of GTP and GDP is mediated by Ggc1p, a member of the mitochondrial carrier family. The physiological role of Ggc1p in <i>S. cerevisiae</i> is probably to transport GTP into mitochondria in exchange for GDP generated in the matrix. <i>ggc1</i>Δ cells exhibit lower levels of GTP and increased levels of GDP in mitochondria, are unable to grow on nonfermentable substrates and lose mtDNA. Because in yeast, succinyl-CoA ligase produces ATP instead of GTP, and the mitochondrial nucleoside diphosphate kinase is localized in the intermembrane space, Ggc1p is the only supplier of mitochondrial GTP required for the maturation of proteins containing Fe-S clusters, such as aconitase [4Fe-4S] and ferredoxin [2Fe-2S]. In this work, it was demonstrated that citrate is a regulator of purified and reconstituted Ggc1p by trans-activating unidirectional transport of GTP across the proteoliposomal membrane. It was also shown that the binding site of Ggc1p for citrate is different from the binding site for the substrate GTP. It is proposed that the citrate-induced GTP uniport (CIGU) mediated by Ggc1p is involved in the homeostasis of the guanine nucleotide pool in the mitochondrial matrix. |
| first_indexed | 2024-03-09T04:15:18Z |
| format | Article |
| id | doaj.art-aa35e0edf64c447faf9856528a37510b |
| institution | Directory Open Access Journal |
| issn | 2309-608X |
| language | English |
| last_indexed | 2024-03-09T04:15:18Z |
| publishDate | 2022-07-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Journal of Fungi |
| spelling | doaj.art-aa35e0edf64c447faf9856528a37510b2023-12-03T13:54:59ZengMDPI AGJournal of Fungi2309-608X2022-07-018879510.3390/jof8080795Citrate Regulates the <i>Saccharomyces cerevisiae</i> Mitochondrial GDP/GTP Carrier (Ggc1p) by Triggering Unidirectional Transport of GTPRoberta Seccia0Silvia De Santis1Maria A. Di Noia2Ferdinando Palmieri3Daniela V. Miniero4Raffaele Marmo5Eleonora Paradies6Antonella Santoro7Ciro L. Pierri8Luigi Palmieri9Carlo M. T. Marobbio10Angelo Vozza11Department of Biosciences, Biotechnologies and Biopharmaceutics, University of Bari, 70125 Bari, ItalyDepartment of Biosciences, Biotechnologies and Biopharmaceutics, University of Bari, 70125 Bari, ItalyDepartment of Biosciences, Biotechnologies and Biopharmaceutics, University of Bari, 70125 Bari, ItalyDepartment of Biosciences, Biotechnologies and Biopharmaceutics, University of Bari, 70125 Bari, ItalyDepartment of Biosciences, Biotechnologies and Biopharmaceutics, University of Bari, 70125 Bari, ItalyDepartment of Biosciences, Biotechnologies and Biopharmaceutics, University of Bari, 70125 Bari, ItalyCNR Institute of Biomembranes, Bioenergetics and Molecular Biotechnologies (IBIOM), 70125 Bari, ItalyDepartment of Biosciences, Biotechnologies and Biopharmaceutics, University of Bari, 70125 Bari, ItalyDepartment of Biosciences, Biotechnologies and Biopharmaceutics, University of Bari, 70125 Bari, ItalyDepartment of Biosciences, Biotechnologies and Biopharmaceutics, University of Bari, 70125 Bari, ItalyDepartment of Biosciences, Biotechnologies and Biopharmaceutics, University of Bari, 70125 Bari, ItalyDepartment of Biosciences, Biotechnologies and Biopharmaceutics, University of Bari, 70125 Bari, ItalyThe yeast mitochondrial transport of GTP and GDP is mediated by Ggc1p, a member of the mitochondrial carrier family. The physiological role of Ggc1p in <i>S. cerevisiae</i> is probably to transport GTP into mitochondria in exchange for GDP generated in the matrix. <i>ggc1</i>Δ cells exhibit lower levels of GTP and increased levels of GDP in mitochondria, are unable to grow on nonfermentable substrates and lose mtDNA. Because in yeast, succinyl-CoA ligase produces ATP instead of GTP, and the mitochondrial nucleoside diphosphate kinase is localized in the intermembrane space, Ggc1p is the only supplier of mitochondrial GTP required for the maturation of proteins containing Fe-S clusters, such as aconitase [4Fe-4S] and ferredoxin [2Fe-2S]. In this work, it was demonstrated that citrate is a regulator of purified and reconstituted Ggc1p by trans-activating unidirectional transport of GTP across the proteoliposomal membrane. It was also shown that the binding site of Ggc1p for citrate is different from the binding site for the substrate GTP. It is proposed that the citrate-induced GTP uniport (CIGU) mediated by Ggc1p is involved in the homeostasis of the guanine nucleotide pool in the mitochondrial matrix.https://www.mdpi.com/2309-608X/8/8/795citrateGDP/GTP carrierGTPFe-S centersmembrane transportmitochondria |
| spellingShingle | Roberta Seccia Silvia De Santis Maria A. Di Noia Ferdinando Palmieri Daniela V. Miniero Raffaele Marmo Eleonora Paradies Antonella Santoro Ciro L. Pierri Luigi Palmieri Carlo M. T. Marobbio Angelo Vozza Citrate Regulates the <i>Saccharomyces cerevisiae</i> Mitochondrial GDP/GTP Carrier (Ggc1p) by Triggering Unidirectional Transport of GTP Journal of Fungi citrate GDP/GTP carrier GTP Fe-S centers membrane transport mitochondria |
| title | Citrate Regulates the <i>Saccharomyces cerevisiae</i> Mitochondrial GDP/GTP Carrier (Ggc1p) by Triggering Unidirectional Transport of GTP |
| title_full | Citrate Regulates the <i>Saccharomyces cerevisiae</i> Mitochondrial GDP/GTP Carrier (Ggc1p) by Triggering Unidirectional Transport of GTP |
| title_fullStr | Citrate Regulates the <i>Saccharomyces cerevisiae</i> Mitochondrial GDP/GTP Carrier (Ggc1p) by Triggering Unidirectional Transport of GTP |
| title_full_unstemmed | Citrate Regulates the <i>Saccharomyces cerevisiae</i> Mitochondrial GDP/GTP Carrier (Ggc1p) by Triggering Unidirectional Transport of GTP |
| title_short | Citrate Regulates the <i>Saccharomyces cerevisiae</i> Mitochondrial GDP/GTP Carrier (Ggc1p) by Triggering Unidirectional Transport of GTP |
| title_sort | citrate regulates the i saccharomyces cerevisiae i mitochondrial gdp gtp carrier ggc1p by triggering unidirectional transport of gtp |
| topic | citrate GDP/GTP carrier GTP Fe-S centers membrane transport mitochondria |
| url | https://www.mdpi.com/2309-608X/8/8/795 |
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