The essential iron-sulfur protein Rli1 is an important target accounting for inhibition of cell growth by reactive oxygen species
Oxidative stress mediated by reactive oxygen species (ROS) is linked to degenerative conditions in humans and damage to an array of cellular components. However, it is unclear which molecular target(s) may be the primary “Achilles’ heel” of organisms, accounting for the inhibitory action of ROS. Rli...
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American Society for Cell Biology
2012
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| Online Access: | https://eprints.nottingham.ac.uk/2341/ |
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| author | Alhebshi, Alawiah Sideri, Theodora C. Holland, Sara L. Avery, Simon V. |
| author_facet | Alhebshi, Alawiah Sideri, Theodora C. Holland, Sara L. Avery, Simon V. |
| author_sort | Alhebshi, Alawiah |
| building | Nottingham Research Data Repository |
| collection | Online Access |
| description | Oxidative stress mediated by reactive oxygen species (ROS) is linked to degenerative conditions in humans and damage to an array of cellular components. However, it is unclear which molecular target(s) may be the primary “Achilles’ heel” of organisms, accounting for the inhibitory action of ROS. Rli1p (ABCE1) is an essential and highly conserved protein of eukaryotes and archaea that requires notoriously ROS-labile cofactors (Fe-S clusters) for its functions in protein synthesis. In this study, we tested the hypothesis that ROS toxicity is caused by Rli1p dysfunction. In addition to being essential, Rli1p activity (in nuclear ribosomal-subunit export) was shown to be impaired by mild oxidative stress in yeast. Furthermore, prooxidant resistance was decreased by RLI1 repression and increased by RLI1 overexpression. This Rlip1 dependency was abolished during anaerobicity and accentuated in cells expressing a FeS cluster–defective Rli1p construct. The protein’s FeS clusters appeared ROS labile during in vitro incubations, but less so in vivo. Instead, it was primarily 55FeS-cluster supply to Rli1p that was defective in prooxidant-exposed cells. The data indicate that, owing to its essential nature but dependency on ROS-labile FeS clusters, Rli1p function is a primary target of ROS action. Such insight could help inform new approaches for combating oxidative stress–related disease. |
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| format | Article |
| id | nottingham-2341 |
| institution | University of Nottingham Malaysia Campus |
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| last_indexed | 2025-11-14T18:17:44Z |
| publishDate | 2012 |
| publisher | American Society for Cell Biology |
| recordtype | eprints |
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| spelling | nottingham-23412020-05-04T16:34:02Z https://eprints.nottingham.ac.uk/2341/ The essential iron-sulfur protein Rli1 is an important target accounting for inhibition of cell growth by reactive oxygen species Alhebshi, Alawiah Sideri, Theodora C. Holland, Sara L. Avery, Simon V. Oxidative stress mediated by reactive oxygen species (ROS) is linked to degenerative conditions in humans and damage to an array of cellular components. However, it is unclear which molecular target(s) may be the primary “Achilles’ heel” of organisms, accounting for the inhibitory action of ROS. Rli1p (ABCE1) is an essential and highly conserved protein of eukaryotes and archaea that requires notoriously ROS-labile cofactors (Fe-S clusters) for its functions in protein synthesis. In this study, we tested the hypothesis that ROS toxicity is caused by Rli1p dysfunction. In addition to being essential, Rli1p activity (in nuclear ribosomal-subunit export) was shown to be impaired by mild oxidative stress in yeast. Furthermore, prooxidant resistance was decreased by RLI1 repression and increased by RLI1 overexpression. This Rlip1 dependency was abolished during anaerobicity and accentuated in cells expressing a FeS cluster–defective Rli1p construct. The protein’s FeS clusters appeared ROS labile during in vitro incubations, but less so in vivo. Instead, it was primarily 55FeS-cluster supply to Rli1p that was defective in prooxidant-exposed cells. The data indicate that, owing to its essential nature but dependency on ROS-labile FeS clusters, Rli1p function is a primary target of ROS action. Such insight could help inform new approaches for combating oxidative stress–related disease. American Society for Cell Biology 2012-09-15 Article PeerReviewed Alhebshi, Alawiah, Sideri, Theodora C., Holland, Sara L. and Avery, Simon V. (2012) The essential iron-sulfur protein Rli1 is an important target accounting for inhibition of cell growth by reactive oxygen species. Molecular Biology of the Cell, 23 (18). pp. 3582-3580. ISSN 1059-1524 http://www.molbiolcell.org/content/23/18/3582. doi:10.1091/mbc.E12-05-0413 doi:10.1091/mbc.E12-05-0413 |
| spellingShingle | Alhebshi, Alawiah Sideri, Theodora C. Holland, Sara L. Avery, Simon V. The essential iron-sulfur protein Rli1 is an important target accounting for inhibition of cell growth by reactive oxygen species |
| title | The essential iron-sulfur protein Rli1 is an important target accounting for inhibition of cell growth by reactive oxygen species |
| title_full | The essential iron-sulfur protein Rli1 is an important target accounting for inhibition of cell growth by reactive oxygen species |
| title_fullStr | The essential iron-sulfur protein Rli1 is an important target accounting for inhibition of cell growth by reactive oxygen species |
| title_full_unstemmed | The essential iron-sulfur protein Rli1 is an important target accounting for inhibition of cell growth by reactive oxygen species |
| title_short | The essential iron-sulfur protein Rli1 is an important target accounting for inhibition of cell growth by reactive oxygen species |
| title_sort | essential iron-sulfur protein rli1 is an important target accounting for inhibition of cell growth by reactive oxygen species |
| url | https://eprints.nottingham.ac.uk/2341/ https://eprints.nottingham.ac.uk/2341/ https://eprints.nottingham.ac.uk/2341/ |