Balanced Ero1 activation and inactivation establishes ER redox homeostasis
The endoplasmic reticulum (ER) provides an environment optimized for oxidative protein folding through the action of Ero1p, which generates disulfide bonds, and Pdi1p, which receives disulfide bonds from Ero1p and transfers them to substrate proteins. Feedback regulation of Ero1p through reduction a...
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| Formatua: | Artikulua |
| Hizkuntza: | en_US |
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Rockefeller University Press, The
2012
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| Sarrera elektronikoa: | http://hdl.handle.net/1721.1/70516 https://orcid.org/0000-0002-1505-0479 |
| _version_ | 1826203948872105984 |
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| author | Kim, Sunghwan Sideris, Polixeni Dionisia Sevier, Carolyn S. Kaiser, Chris |
| author2 | Massachusetts Institute of Technology. Department of Biology |
| author_facet | Massachusetts Institute of Technology. Department of Biology Kim, Sunghwan Sideris, Polixeni Dionisia Sevier, Carolyn S. Kaiser, Chris |
| author_sort | Kim, Sunghwan |
| collection | MIT |
| description | The endoplasmic reticulum (ER) provides an environment optimized for oxidative protein folding through the action of Ero1p, which generates disulfide bonds, and Pdi1p, which receives disulfide bonds from Ero1p and transfers them to substrate proteins. Feedback regulation of Ero1p through reduction and oxidation of regulatory bonds within Ero1p is essential for maintaining the proper redox balance in the ER. In this paper, we show that Pdi1p is the key regulator of Ero1p activity. Reduced Pdi1p resulted in the activation of Ero1p by direct reduction of Ero1p regulatory bonds. Conversely, upon depletion of thiol substrates and accumulation of oxidized Pdi1p, Ero1p was inactivated by both autonomous oxidation and Pdi1p-mediated oxidation of Ero1p regulatory bonds. Pdi1p responded to the availability of free thiols and the relative levels of reduced and oxidized glutathione in the ER to control Ero1p activity and ensure that cells generate the minimum number of disulfide bonds needed for efficient oxidative protein folding. |
| first_indexed | 2024-09-23T12:45:58Z |
| format | Article |
| id | mit-1721.1/70516 |
| institution | Massachusetts Institute of Technology |
| language | en_US |
| last_indexed | 2024-09-23T12:45:58Z |
| publishDate | 2012 |
| publisher | Rockefeller University Press, The |
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| spelling | mit-1721.1/705162022-09-28T09:55:32Z Balanced Ero1 activation and inactivation establishes ER redox homeostasis Kim, Sunghwan Sideris, Polixeni Dionisia Sevier, Carolyn S. Kaiser, Chris Massachusetts Institute of Technology. Department of Biology Sunghwan, Kim Kim, Sunghwan Sideris, Polixeni Dionisia Sevier, Carolyn S. Kaiser, Chris The endoplasmic reticulum (ER) provides an environment optimized for oxidative protein folding through the action of Ero1p, which generates disulfide bonds, and Pdi1p, which receives disulfide bonds from Ero1p and transfers them to substrate proteins. Feedback regulation of Ero1p through reduction and oxidation of regulatory bonds within Ero1p is essential for maintaining the proper redox balance in the ER. In this paper, we show that Pdi1p is the key regulator of Ero1p activity. Reduced Pdi1p resulted in the activation of Ero1p by direct reduction of Ero1p regulatory bonds. Conversely, upon depletion of thiol substrates and accumulation of oxidized Pdi1p, Ero1p was inactivated by both autonomous oxidation and Pdi1p-mediated oxidation of Ero1p regulatory bonds. Pdi1p responded to the availability of free thiols and the relative levels of reduced and oxidized glutathione in the ER to control Ero1p activity and ensure that cells generate the minimum number of disulfide bonds needed for efficient oxidative protein folding. National Institutes of Health (U.S.) (GM46941) 2012-05-04T20:57:47Z 2012-05-04T20:57:47Z 2012-03 2011-10 Article http://purl.org/eprint/type/JournalArticle 0021-9525 1540-8140 http://hdl.handle.net/1721.1/70516 Kim, S. et al. “Balanced Ero1 Activation and Inactivation Establishes ER Redox Homeostasis.” The Journal of Cell Biology 196.6 (2012): 713–725. Web. 4 May 2012. https://orcid.org/0000-0002-1505-0479 en_US http://dx.doi.org/10.1083/jcb.201110090 Journal of Cell Biology Creative Commons Attribution-Noncommercial-Share Alike 3.0 Unported http://creativecommons.org/licenses/by-nc-sa/3.0/ application/pdf Rockefeller University Press, The Rockefeller UP |
| spellingShingle | Kim, Sunghwan Sideris, Polixeni Dionisia Sevier, Carolyn S. Kaiser, Chris Balanced Ero1 activation and inactivation establishes ER redox homeostasis |
| title | Balanced Ero1 activation and inactivation establishes ER redox homeostasis |
| title_full | Balanced Ero1 activation and inactivation establishes ER redox homeostasis |
| title_fullStr | Balanced Ero1 activation and inactivation establishes ER redox homeostasis |
| title_full_unstemmed | Balanced Ero1 activation and inactivation establishes ER redox homeostasis |
| title_short | Balanced Ero1 activation and inactivation establishes ER redox homeostasis |
| title_sort | balanced ero1 activation and inactivation establishes er redox homeostasis |
| url | http://hdl.handle.net/1721.1/70516 https://orcid.org/0000-0002-1505-0479 |
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