TOR Signaling Couples Oxygen Sensing to Lifespan in C. elegans
Summary: 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 regulation of the nutrient-sensing kinase target...
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doaj-a849073b65024289ae3a017325da3ae42020-11-25T00:27:23ZengElsevierCell Reports2211-12472014-10-0191915TOR Signaling Couples Oxygen Sensing to Lifespan in C. elegansMichael Schieber0Navdeep S. Chandel1Department of Medicine, Northwestern University Feinberg School of Medicine, Chicago, IL 60611, USADepartment of Medicine, Northwestern University Feinberg School of Medicine, Chicago, IL 60611, USA; Corresponding authorSummary: 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 regulation of the nutrient-sensing kinase target of rapamycin (TOR) and its upstream activator, RHEB-1. The increase in lifespan during hypoxia requires the intestinal 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 is required for lifespan under hypoxia. These results indicate mitochondrial ROS-dependent TOR signaling integrates metabolic adaptations in order to confer survival under hypoxia. : Metazoans adapt to low-oxygen environments (hypoxia) through activation of stress-response pathways. Schieber and Chandel now report on a hypoxia response that extends lifespan in C. elegans. Under hypoxia, increased levels of mitochondrial ROS upregulate the intestinal glutathione S-transferase GSTO-1 to extend lifespan. The nutrient-signaling kinase TOR and the intestinal GATA-type transcription factor ELT-2 are required for GSTO-1 induction. These results uncover a mechanism for adaptation to hypoxia and support a model whereby increased mitochondrial ROS prevent age-related pathologies.http://www.sciencedirect.com/science/article/pii/S2211124714007670 |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Michael Schieber Navdeep S. Chandel |
spellingShingle |
Michael Schieber Navdeep S. Chandel TOR Signaling Couples Oxygen Sensing to Lifespan in C. elegans Cell Reports |
author_facet |
Michael Schieber Navdeep S. Chandel |
author_sort |
Michael Schieber |
title |
TOR Signaling Couples Oxygen Sensing to Lifespan in C. elegans |
title_short |
TOR Signaling Couples Oxygen Sensing to Lifespan in C. elegans |
title_full |
TOR Signaling Couples Oxygen Sensing to Lifespan in C. elegans |
title_fullStr |
TOR Signaling Couples Oxygen Sensing to Lifespan in C. elegans |
title_full_unstemmed |
TOR Signaling Couples Oxygen Sensing to Lifespan in C. elegans |
title_sort |
tor signaling couples oxygen sensing to lifespan in c. elegans |
publisher |
Elsevier |
series |
Cell Reports |
issn |
2211-1247 |
publishDate |
2014-10-01 |
description |
Summary: 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 regulation of the nutrient-sensing kinase target of rapamycin (TOR) and its upstream activator, RHEB-1. The increase in lifespan during hypoxia requires the intestinal 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 is required for lifespan under hypoxia. These results indicate mitochondrial ROS-dependent TOR signaling integrates metabolic adaptations in order to confer survival under hypoxia. : Metazoans adapt to low-oxygen environments (hypoxia) through activation of stress-response pathways. Schieber and Chandel now report on a hypoxia response that extends lifespan in C. elegans. Under hypoxia, increased levels of mitochondrial ROS upregulate the intestinal glutathione S-transferase GSTO-1 to extend lifespan. The nutrient-signaling kinase TOR and the intestinal GATA-type transcription factor ELT-2 are required for GSTO-1 induction. These results uncover a mechanism for adaptation to hypoxia and support a model whereby increased mitochondrial ROS prevent age-related pathologies. |
url |
http://www.sciencedirect.com/science/article/pii/S2211124714007670 |
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