NQO1 binds and supports SIRT1 function
<jats:title>Abstract</jats:title><jats:p>Silent information regulator 2-related enzyme 1 (SIRT1) is an NAD<jats:sup>+</jats:sup>-dependent class III deacetylase and a key component of the cellular metabolic sensing pathway. The requirement of NAD<jats:sup>+</ja...
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| Format: | Article |
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Frontiers
2021
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| Online Access: | https://hdl.handle.net/1721.1/137228 |
| _version_ | 1826208982344138752 |
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| author | Tsvetkov, Peter Adler, Julia Adamovich, Yaarit Asher, Gad Reuven, Nina Shaul, Yosef |
| author2 | Whitehead Institute for Biomedical Research |
| author_facet | Whitehead Institute for Biomedical Research Tsvetkov, Peter Adler, Julia Adamovich, Yaarit Asher, Gad Reuven, Nina Shaul, Yosef |
| author_sort | Tsvetkov, Peter |
| collection | MIT |
| description | <jats:title>Abstract</jats:title><jats:p>Silent information regulator 2-related enzyme 1 (SIRT1) is an NAD<jats:sup>+</jats:sup>-dependent class III deacetylase and a key component of the cellular metabolic sensing pathway. The requirement of NAD<jats:sup>+</jats:sup> for SIRT1 activity led us to assume that NQO1, an NADH oxidoreductase producing NAD<jats:sup>+</jats:sup>, regulates SIRT1 activity. We show here that SIRT1 is capable of increasing NQO1 (NAD(P)H Dehydrogenase Quinone 1) transcription and protein levels. NQO1 physically interacts with SIRT1 but not with an enzymatically dead SIRT1 H363Y mutant. The interaction of NQO1 with SIRT1 is markedly increased under mitochondrial inhibition. Interestingly, under this condition the nuclear pool of NQO1 is elevated. Depletion of NQO1 compromises the role of SIRT1 in inducing transcription of several target genes and eliminates the protective role of SIRT1 following mitochondrial inhibition. Our results suggest that SIRT1 and NQO1 form a regulatory loop where SIRT1 regulates NQO1 expression and NQO1 binds and mediates the protective role of SIRT1 during mitochondrial stress. The interplay between an NADH oxidoreductase enzyme and an NAD<jats:sup>+</jats:sup> dependent deacetylase may act as a rheostat in sensing mitochondrial stress.</jats:p> |
| first_indexed | 2024-09-23T14:15:31Z |
| format | Article |
| id | mit-1721.1/137228 |
| institution | Massachusetts Institute of Technology |
| last_indexed | 2024-09-23T14:15:31Z |
| publishDate | 2021 |
| publisher | Frontiers |
| record_format | dspace |
| spelling | mit-1721.1/1372282023-02-10T21:09:56Z NQO1 binds and supports SIRT1 function Tsvetkov, Peter Adler, Julia Adamovich, Yaarit Asher, Gad Reuven, Nina Shaul, Yosef Whitehead Institute for Biomedical Research <jats:title>Abstract</jats:title><jats:p>Silent information regulator 2-related enzyme 1 (SIRT1) is an NAD<jats:sup>+</jats:sup>-dependent class III deacetylase and a key component of the cellular metabolic sensing pathway. The requirement of NAD<jats:sup>+</jats:sup> for SIRT1 activity led us to assume that NQO1, an NADH oxidoreductase producing NAD<jats:sup>+</jats:sup>, regulates SIRT1 activity. We show here that SIRT1 is capable of increasing NQO1 (NAD(P)H Dehydrogenase Quinone 1) transcription and protein levels. NQO1 physically interacts with SIRT1 but not with an enzymatically dead SIRT1 H363Y mutant. The interaction of NQO1 with SIRT1 is markedly increased under mitochondrial inhibition. Interestingly, under this condition the nuclear pool of NQO1 is elevated. Depletion of NQO1 compromises the role of SIRT1 in inducing transcription of several target genes and eliminates the protective role of SIRT1 following mitochondrial inhibition. Our results suggest that SIRT1 and NQO1 form a regulatory loop where SIRT1 regulates NQO1 expression and NQO1 binds and mediates the protective role of SIRT1 during mitochondrial stress. The interplay between an NADH oxidoreductase enzyme and an NAD<jats:sup>+</jats:sup> dependent deacetylase may act as a rheostat in sensing mitochondrial stress.</jats:p> 2021-11-03T15:59:19Z 2021-11-03T15:59:19Z 2021-06-21 Article http://purl.org/eprint/type/JournalArticle https://hdl.handle.net/1721.1/137228 Tsvetkov, Peter, Adler, Julia, Adamovich, Yaarit, Asher, Gad, Reuven, Nina et al. 2021. "NQO1 binds and supports SIRT1 function." Frontiers in Pharmacology. 10.1101/139907 Frontiers in Pharmacology Creative Commons Attribution 4.0 International license https://creativecommons.org/licenses/by/4.0/ application/pdf Frontiers Frontiers |
| spellingShingle | Tsvetkov, Peter Adler, Julia Adamovich, Yaarit Asher, Gad Reuven, Nina Shaul, Yosef NQO1 binds and supports SIRT1 function |
| title | NQO1 binds and supports SIRT1 function |
| title_full | NQO1 binds and supports SIRT1 function |
| title_fullStr | NQO1 binds and supports SIRT1 function |
| title_full_unstemmed | NQO1 binds and supports SIRT1 function |
| title_short | NQO1 binds and supports SIRT1 function |
| title_sort | nqo1 binds and supports sirt1 function |
| url | https://hdl.handle.net/1721.1/137228 |
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