Unknown

Dataset Information

0

NHR-49/HNF4 integrates regulation of fatty acid metabolism with a protective transcriptional response to oxidative stress and fasting.


ABSTRACT: Endogenous and exogenous stresses elicit transcriptional responses that limit damage and promote cell/organismal survival. Like its mammalian counterparts, hepatocyte nuclear factor 4 (HNF4) and peroxisome proliferator-activated receptor ? (PPAR?), Caenorhabditis elegans NHR-49 is a well-established regulator of lipid metabolism. Here, we reveal that NHR-49 is essential to activate a transcriptional response common to organic peroxide and fasting, which includes the pro-longevity gene fmo-2/flavin-containing monooxygenase. These NHR-49-dependent, stress-responsive genes are also upregulated in long-lived glp-1/notch receptor mutants, with two of them making critical contributions to the oxidative stress resistance of wild-type and long-lived glp-1 mutants worms. Similar to its role in lipid metabolism, NHR-49 requires the mediator subunit mdt-15 to promote stress-induced gene expression. However, NHR-49 acts independently from the transcription factor hlh-30/TFEB that also promotes fmo-2 expression. We show that activation of the p38 MAPK, PMK-1, which is important for adaptation to a variety of stresses, is also important for peroxide-induced expression of a subset of NHR-49-dependent genes that includes fmo-2. However, organic peroxide increases NHR-49 protein levels, by a posttranscriptional mechanism that does not require PMK-1 activation. Together, these findings establish a new role for the HNF4/PPAR?-related NHR-49 as a stress-activated regulator of cytoprotective gene expression.

SUBMITTER: Goh GYS 

PROVIDER: S-EPMC5946062 | biostudies-literature | 2018 Jun

REPOSITORIES: biostudies-literature

altmetric image

Publications

NHR-49/HNF4 integrates regulation of fatty acid metabolism with a protective transcriptional response to oxidative stress and fasting.

Goh Grace Y S GYS   Winter Johnathan J JJ   Bhanshali Forum F   Doering Kelsie R S KRS   Lai Regina R   Lee Kayoung K   Veal Elizabeth A EA   Taubert Stefan S  

Aging cell 20180305 3


Endogenous and exogenous stresses elicit transcriptional responses that limit damage and promote cell/organismal survival. Like its mammalian counterparts, hepatocyte nuclear factor 4 (HNF4) and peroxisome proliferator-activated receptor α (PPARα), Caenorhabditis elegans NHR-49 is a well-established regulator of lipid metabolism. Here, we reveal that NHR-49 is essential to activate a transcriptional response common to organic peroxide and fasting, which includes the pro-longevity gene fmo-2/flav  ...[more]

Similar Datasets

2018-03-05 | GSE107799 | GEO
| PRJNA421426 | ENA
| S-EPMC3057950 | biostudies-literature
| S-EPMC547972 | biostudies-literature
| S-EPMC5595674 | biostudies-literature
| S-EPMC4256272 | biostudies-literature
| S-EPMC5794426 | biostudies-literature
2012-03-15 | GSE34856 | GEO
| S-EPMC8291716 | biostudies-literature
| S-EPMC6155532 | biostudies-literature