The unfolded protein response has a protective role in yeast models of classic galactosemia
Classic galactosemia is a human autosomal recessive disorder caused by mutations in the GALT gene (GAL7 in yeast), which encodes the enzyme galactose-1-phosphate uridyltransferase. Here we show that the unfolded protein response pathway is triggered by galactose in two yeast models of galactosemia:...
| Main Authors: | , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
The Company of Biologists
2014-01-01
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| Series: | Disease Models & Mechanisms |
| Subjects: | |
| Online Access: | http://dmm.biologists.org/content/7/1/55 |
| _version_ | 1819011558494175232 |
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| author | Evandro A. De-Souza Felipe S. A. Pimentel Caio M. Machado Larissa S. Martins Wagner S. da-Silva Mónica Montero-Lomelí Claudio A. Masuda |
| author_facet | Evandro A. De-Souza Felipe S. A. Pimentel Caio M. Machado Larissa S. Martins Wagner S. da-Silva Mónica Montero-Lomelí Claudio A. Masuda |
| author_sort | Evandro A. De-Souza |
| collection | DOAJ |
| description | Classic galactosemia is a human autosomal recessive disorder caused by mutations in the GALT gene (GAL7 in yeast), which encodes the enzyme galactose-1-phosphate uridyltransferase. Here we show that the unfolded protein response pathway is triggered by galactose in two yeast models of galactosemia: lithium-treated cells and the gal7Δ mutant. The synthesis of galactose-1-phosphate is essential to trigger the unfolded protein response under these conditions because the deletion of the galactokinase-encoding gene GAL1 completely abolishes unfolded protein response activation and galactose toxicity. Impairment of the unfolded protein response in both yeast models makes cells even more sensitive to galactose, unmasking its cytotoxic effect. These results indicate that endoplasmic reticulum stress is induced under galactosemic conditions and underscores the importance of the unfolded protein response pathway to cellular adaptation in these models of classic galactosemia. |
| first_indexed | 2024-12-21T01:30:04Z |
| format | Article |
| id | doaj.art-0d328464420d429e8395af3ccb6fae5a |
| institution | Directory Open Access Journal |
| issn | 1754-8403 1754-8411 |
| language | English |
| last_indexed | 2024-12-21T01:30:04Z |
| publishDate | 2014-01-01 |
| publisher | The Company of Biologists |
| record_format | Article |
| series | Disease Models & Mechanisms |
| spelling | doaj.art-0d328464420d429e8395af3ccb6fae5a2022-12-21T19:20:24ZengThe Company of BiologistsDisease Models & Mechanisms1754-84031754-84112014-01-0171556110.1242/dmm.012641012641The unfolded protein response has a protective role in yeast models of classic galactosemiaEvandro A. De-SouzaFelipe S. A. PimentelCaio M. MachadoLarissa S. MartinsWagner S. da-SilvaMónica Montero-LomelíClaudio A. MasudaClassic galactosemia is a human autosomal recessive disorder caused by mutations in the GALT gene (GAL7 in yeast), which encodes the enzyme galactose-1-phosphate uridyltransferase. Here we show that the unfolded protein response pathway is triggered by galactose in two yeast models of galactosemia: lithium-treated cells and the gal7Δ mutant. The synthesis of galactose-1-phosphate is essential to trigger the unfolded protein response under these conditions because the deletion of the galactokinase-encoding gene GAL1 completely abolishes unfolded protein response activation and galactose toxicity. Impairment of the unfolded protein response in both yeast models makes cells even more sensitive to galactose, unmasking its cytotoxic effect. These results indicate that endoplasmic reticulum stress is induced under galactosemic conditions and underscores the importance of the unfolded protein response pathway to cellular adaptation in these models of classic galactosemia.http://dmm.biologists.org/content/7/1/55YeastGalactosemiaUPRLithiumGalactose |
| spellingShingle | Evandro A. De-Souza Felipe S. A. Pimentel Caio M. Machado Larissa S. Martins Wagner S. da-Silva Mónica Montero-Lomelí Claudio A. Masuda The unfolded protein response has a protective role in yeast models of classic galactosemia Disease Models & Mechanisms Yeast Galactosemia UPR Lithium Galactose |
| title | The unfolded protein response has a protective role in yeast models of classic galactosemia |
| title_full | The unfolded protein response has a protective role in yeast models of classic galactosemia |
| title_fullStr | The unfolded protein response has a protective role in yeast models of classic galactosemia |
| title_full_unstemmed | The unfolded protein response has a protective role in yeast models of classic galactosemia |
| title_short | The unfolded protein response has a protective role in yeast models of classic galactosemia |
| title_sort | unfolded protein response has a protective role in yeast models of classic galactosemia |
| topic | Yeast Galactosemia UPR Lithium Galactose |
| url | http://dmm.biologists.org/content/7/1/55 |
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