Targeting Copper Homeostasis Improves Functioning of <i>vps13</i>Δ Yeast Mutant Cells, a Model of <i>VPS13</i>-Related Diseases
Ion homeostasis is crucial for organism functioning, and its alterations may cause diseases. For example, copper insufficiency and overload are associated with Menkes and Wilson’s diseases, respectively, and iron imbalance is observed in Parkinson’s and Alzheimer’s diseases. To better understand hum...
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MDPI AG
2021-02-01
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| Series: | International Journal of Molecular Sciences |
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| Online Access: | https://www.mdpi.com/1422-0067/22/5/2248 |
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| author | Piotr Soczewka Déborah Tribouillard-Tanvier Jean-Paul di Rago Teresa Zoladek Joanna Kaminska |
| author_facet | Piotr Soczewka Déborah Tribouillard-Tanvier Jean-Paul di Rago Teresa Zoladek Joanna Kaminska |
| author_sort | Piotr Soczewka |
| collection | DOAJ |
| description | Ion homeostasis is crucial for organism functioning, and its alterations may cause diseases. For example, copper insufficiency and overload are associated with Menkes and Wilson’s diseases, respectively, and iron imbalance is observed in Parkinson’s and Alzheimer’s diseases. To better understand human diseases, <i>Saccharomyces cerevisiae</i> yeast are used as a model organism. In our studies, we used the <i>vps13</i>Δ yeast strain as a model of rare neurological diseases caused by mutations in <i>VPS13A</i>–<i>D</i> genes. In this work, we show that overexpression of genes encoding copper transporters, <i>CTR1</i>, <i>CTR3</i>, and <i>CCC2</i>, or the addition of copper salt to the medium, improved functioning of the <i>vps13</i>Δ mutant. We show that their mechanism of action, at least partially, depends on increasing iron content in the cells by the copper-dependent iron uptake system. Finally, we present that treatment with copper ionophores, disulfiram, elesclomol, and sodium pyrithione, also resulted in alleviation of the defects observed in <i>vps13</i>Δ cells. Our study points at copper and iron homeostasis as a potential therapeutic target for further investigation in higher eukaryotic models of <i>VPS13</i>-related diseases. |
| first_indexed | 2024-03-09T00:35:49Z |
| format | Article |
| id | doaj.art-bdbdcf626d534eb38edb579cfb27c6be |
| institution | Directory Open Access Journal |
| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-03-09T00:35:49Z |
| publishDate | 2021-02-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | International Journal of Molecular Sciences |
| spelling | doaj.art-bdbdcf626d534eb38edb579cfb27c6be2023-12-11T18:13:42ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672021-02-01225224810.3390/ijms22052248Targeting Copper Homeostasis Improves Functioning of <i>vps13</i>Δ Yeast Mutant Cells, a Model of <i>VPS13</i>-Related DiseasesPiotr Soczewka0Déborah Tribouillard-Tanvier1Jean-Paul di Rago2Teresa Zoladek3Joanna Kaminska4Institute of Biochemistry and Biophysics, Polish Academy of Sciences, 02-106 Warsaw, PolandIBGC, UMR 5095, CNRS, Université de Bordeaux, F-33000 Bordeaux, FranceIBGC, UMR 5095, CNRS, Université de Bordeaux, F-33000 Bordeaux, FranceInstitute of Biochemistry and Biophysics, Polish Academy of Sciences, 02-106 Warsaw, PolandInstitute of Biochemistry and Biophysics, Polish Academy of Sciences, 02-106 Warsaw, PolandIon homeostasis is crucial for organism functioning, and its alterations may cause diseases. For example, copper insufficiency and overload are associated with Menkes and Wilson’s diseases, respectively, and iron imbalance is observed in Parkinson’s and Alzheimer’s diseases. To better understand human diseases, <i>Saccharomyces cerevisiae</i> yeast are used as a model organism. In our studies, we used the <i>vps13</i>Δ yeast strain as a model of rare neurological diseases caused by mutations in <i>VPS13A</i>–<i>D</i> genes. In this work, we show that overexpression of genes encoding copper transporters, <i>CTR1</i>, <i>CTR3</i>, and <i>CCC2</i>, or the addition of copper salt to the medium, improved functioning of the <i>vps13</i>Δ mutant. We show that their mechanism of action, at least partially, depends on increasing iron content in the cells by the copper-dependent iron uptake system. Finally, we present that treatment with copper ionophores, disulfiram, elesclomol, and sodium pyrithione, also resulted in alleviation of the defects observed in <i>vps13</i>Δ cells. Our study points at copper and iron homeostasis as a potential therapeutic target for further investigation in higher eukaryotic models of <i>VPS13</i>-related diseases.https://www.mdpi.com/1422-0067/22/5/2248yeast modelneurodegeneration<i>VPS13</i><i>CTR1</i><i>CCC2</i><i>FET3</i> |
| spellingShingle | Piotr Soczewka Déborah Tribouillard-Tanvier Jean-Paul di Rago Teresa Zoladek Joanna Kaminska Targeting Copper Homeostasis Improves Functioning of <i>vps13</i>Δ Yeast Mutant Cells, a Model of <i>VPS13</i>-Related Diseases International Journal of Molecular Sciences yeast model neurodegeneration <i>VPS13</i> <i>CTR1</i> <i>CCC2</i> <i>FET3</i> |
| title | Targeting Copper Homeostasis Improves Functioning of <i>vps13</i>Δ Yeast Mutant Cells, a Model of <i>VPS13</i>-Related Diseases |
| title_full | Targeting Copper Homeostasis Improves Functioning of <i>vps13</i>Δ Yeast Mutant Cells, a Model of <i>VPS13</i>-Related Diseases |
| title_fullStr | Targeting Copper Homeostasis Improves Functioning of <i>vps13</i>Δ Yeast Mutant Cells, a Model of <i>VPS13</i>-Related Diseases |
| title_full_unstemmed | Targeting Copper Homeostasis Improves Functioning of <i>vps13</i>Δ Yeast Mutant Cells, a Model of <i>VPS13</i>-Related Diseases |
| title_short | Targeting Copper Homeostasis Improves Functioning of <i>vps13</i>Δ Yeast Mutant Cells, a Model of <i>VPS13</i>-Related Diseases |
| title_sort | targeting copper homeostasis improves functioning of i vps13 i δ yeast mutant cells a model of i vps13 i related diseases |
| topic | yeast model neurodegeneration <i>VPS13</i> <i>CTR1</i> <i>CCC2</i> <i>FET3</i> |
| url | https://www.mdpi.com/1422-0067/22/5/2248 |
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