TOR signaling couples oxygen sensing to lifespan in C.elegans

Michael Schieber, Navdeep Chandel*

*Corresponding author for this work

Research output: Contribution to journalArticle

38 Citations (Scopus)

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 languageEnglish (US)
Pages (from-to)9-15
Number of pages7
JournalCell reports
Volume9
Issue number1
DOIs
StatePublished - Oct 9 2014

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Sirolimus
Oxygen
Reactive Oxygen Species
GATA Transcription Factors
Glutathione Transferase
Nutrients
GATA2 Transcription Factor
Phosphotransferases
Chemical activation
RNA
RNA Sequence Analysis
Hypoxia
Food

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

Cite this

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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.",
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TOR signaling couples oxygen sensing to lifespan in C.elegans. / Schieber, Michael; Chandel, Navdeep.

In: Cell reports, Vol. 9, No. 1, 09.10.2014, p. 9-15.

Research output: Contribution to journalArticle

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