TOR signaling couples oxygen sensing to lifespan in C.elegans

Michael Schieber; Navdeep S. Chandel

doi:10.1016/j.celrep.2014.08.075

TOR signaling couples oxygen sensing to lifespan in C.elegans

Michael Schieber, Navdeep S. Chandel^*

^*Corresponding author for this work

Medicine, Pulmonary Division

Research output: Contribution to journal › Article › peer-review

59 Scopus citations

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	https://doi.org/10.1016/j.celrep.2014.08.075
State	Published - Oct 9 2014

ASJC Scopus subject areas

Biochemistry, Genetics and Molecular Biology(all)

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title = "TOR signaling couples oxygen sensing to lifespan in C.elegans",

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.",

author = "Michael Schieber and Chandel, {Navdeep S.}",

note = "Funding Information: 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. Publisher Copyright: {\textcopyright} 2014 The Authors.",

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doi = "10.1016/j.celrep.2014.08.075",

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AU - Schieber, Michael

AU - Chandel, Navdeep S.

N1 - Funding Information: 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. Publisher Copyright: © 2014 The Authors.

PY - 2014/10/9

Y1 - 2014/10/9

N2 - 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.

AB - 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

Abstract

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