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...
| Main Authors: | , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
MDPI AG
2021-02-01
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| Series: | International Journal of Molecular Sciences |
| Subjects: | |
| Online Access: | https://www.mdpi.com/1422-0067/22/5/2248 |
| Summary: | 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. |
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| ISSN: | 1661-6596 1422-0067 |