|
|
|
|
LEADER |
01942nam a2200253Ia 4500 |
001 |
10.1016-j.isci.2022.104571 |
008 |
220706s2022 CNT 000 0 und d |
020 |
|
|
|a 25890042 (ISSN)
|
245 |
1 |
0 |
|a SKN-1 regulates stress resistance downstream of amino catabolism pathways
|
260 |
|
0 |
|b Elsevier Inc.
|c 2022
|
856 |
|
|
|z View Fulltext in Publisher
|u https://doi.org/10.1016/j.isci.2022.104571
|
520 |
3 |
|
|a The deleterious potential to generate oxidative stress is a fundamental challenge to metabolism. The oxidative stress response transcription factor, SKN-1/NRF2, can sense and respond to changes in metabolic state, although the mechanism and consequences of this remain unknown. Here, we performed a genetic screen in C. elegans targeting amino acid catabolism and identified multiple metabolic pathways as regulators of SKN-1 activity. We found that knockdown of the conserved amidohydrolase T12A2.1/amdh-1 activates a unique subset of SKN-1 regulated genes. Interestingly, this transcriptional program is independent of canonical P38-MAPK signaling components but requires ELT-3, NHR-49 and MDT-15. This activation of SKN-1 is dependent on upstream histidine catabolism genes HALY-1 and Y51H4A.7/UROC-1 and may occur through accumulation of a catabolite, 4-imidazolone-5-propanoate. Activating SKN-1 results in increased oxidative stress resistance but decreased survival to heat stress. Together, our data suggest that SKN-1 acts downstream of key catabolic pathways to influence physiology and stress resistance. © 2022 The Author(s)
|
650 |
0 |
4 |
|a Biological sciences
|
650 |
0 |
4 |
|a Molecular biology
|
650 |
0 |
4 |
|a Transcriptomics
|
700 |
1 |
|
|a Bar-Ziv, R.
|e author
|
700 |
1 |
|
|a Bolas, T.
|e author
|
700 |
1 |
|
|a Dillin, A.
|e author
|
700 |
1 |
|
|a Frankino, P.A.
|e author
|
700 |
1 |
|
|a Gildea, H.K.
|e author
|
700 |
1 |
|
|a Higuchi-Sanabria, R.
|e author
|
700 |
1 |
|
|a Siddiqi, T.F.
|e author
|
700 |
1 |
|
|a Zhang, H.
|e author
|
773 |
|
|
|t iScience
|