Abstract
Metazoans adapt to a low-oxygen environment (hypoxia) through activation of stress-response pathways. Here, we report that transient hypoxia exposure extends lifespan in C.elegans through mitochondrial reactive oxygen species (ROS)-dependent regulationof the nutrient-sensing kinase target of rapamycin(TOR) and its upstream activator, RHEB-1. The increase in lifespan during hypoxia requires theintestinal GATA-type transcription factor ELT-2 downstream of TOR signaling. Using RNA sequencing (RNA-seq), we describe an ELT-2-dependent hypoxia response that includes an intestinal glutathione S-transferase, GSTO-1, and uncover that GSTO-1 isrequired for lifespan under hypoxia. These resultsindicate mitochondrial ROS-dependent TOR signaling integrates metabolic adaptations in order to confer survival under hypoxia.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 9-15 |
| Number of pages | 7 |
| Journal | Cell reports |
| Volume | 9 |
| Issue number | 1 |
| DOIs | |
| State | Published - Oct 9 2014 |
Funding
The Chicago Biomedical Consortium as well as NIH grants T32HL076139 (M.S.) and 1R01HL122062-01 (N.S.C.) supported this work. We thank Matthew J. Schipma at NGS Core Facility at Feinberg School of Medicine, Northwestern University for RNA-seq analysis. We are grateful to Dr. Manu Jain for assistance with the statistical analysis of longevity assays in this article.
ASJC Scopus subject areas
- General Biochemistry, Genetics and Molecular Biology