TOR signaling couples oxygen sensing to lifespan in C. elegans

Cell Reports
Michael Schieber, Navdeep S Chandel


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.


Mar 15, 2015·International Journal of Molecular Sciences·Adam BeachVladimir I Titorenko
Jun 24, 2015·The Journal of Cell Biology·Lilian T Lamech, Cole M Haynes
Jan 19, 2016·Molecular Aspects of Medicine·Gregory B WaypaPaul T Schumacker
Mar 5, 2016·Molecular Cell·Yi-Fan Lin, Cole M Haynes
Oct 27, 2015·Cell·Gerald S Shadel, Tamas L Horvath
Mar 20, 2016·Archives of Toxicology·Philip G Board, Deepthi Menon
Mar 24, 2016·Trends in Cell Biology·Ulrike TopfAgnieszka Chacinska
Apr 11, 2015·Biochimica Et Biophysica Acta·Anna M Schulz, Cole M Haynes
Dec 30, 2014·Current Opinion in Cell Biology·Virginija Jovaisaite, Johan Auwerx
May 8, 2016·Free Radical Biology & Medicine·Lauren Diebold, Navdeep S Chandel
Jul 4, 2016·Zoology : Analysis of Complex Systems, ZACS·Wentao YangHinrich Schulenburg
Nov 7, 2017·FEBS Letters·Rhoda Stefanatos, Alberto Sanz
Nov 23, 2017·Nature Reviews. Molecular Cell Biology·Tomer Shpilka, Cole M Haynes
Feb 21, 2019·Oncotarget·Laurent M PaardekooperGeert van den Bogaart
Feb 2, 2019·Frontiers in Aging Neuroscience·Paloma García-CasasJavier Alvarez
May 22, 2020·Nanoscale Research Letters·Zhongjie YuPeifeng Li
May 17, 2017·Frontiers in Molecular Neuroscience·Francois Mouton-LigerOlga Corti
Aug 12, 2019·Environmental Monitoring and Assessment·Wafa BoulajfeneSabiha Zouari-Tlig
Nov 8, 2019·Biochemical Society Transactions·Megan L StokerKarl J Morten
Sep 10, 2020·Genes·Ivana Bjedov, Charalampos Rallis
Oct 4, 2020·Nature Communications·Thomas HeimbucherColeen T Murphy
Sep 30, 2020·The Journal of Experimental Biology·Danielle M PolanSavraj Grewal


Dec 2, 1993·Nature·C KenyonR Tabtiang
Jun 5, 2003·The Journal of Biological Chemistry·Andrew M ArshamM Celeste Simon
Jul 4, 2003·The Journal of Clinical Investigation·Guénahel H DanetM Celeste Simon
Jun 10, 2004·Current Biology : CB·Pankaj KapahiSeymour Benzer
Sep 27, 2005·The Journal of Biological Chemistry·Dos D Sarbassov, David M Sabatini
Nov 23, 2006·Developmental Biology·James D McGheeA Gordon Robertson
Dec 5, 2006·Genes & Development·Scott M WelfordAmato J Giaccia
Mar 1, 2007·JAMA : the Journal of the American Medical Association·Goran BjelakovicChristian Gluud
Aug 8, 2007·Gene·Hiroshi QadotaKozo Kaibuchi
Sep 29, 2007·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Cora BurmeisterEva Liebau
Dec 1, 2007·WormBook : the Online Review of C. Elegans Biology·James D McGhee
May 24, 2008·Molecular Cell·William G Kaelin, Peter J Ratcliffe
Oct 11, 2008·Nature Reviews. Cancer·Bradly G Wouters, Marianne Koritzinsky
Feb 7, 2009·PLoS Genetics·Jeremy M Van Raamsdonk, Siegfried Hekimi
Apr 18, 2009·Science·Ranjana MehtaMatt Kaeberlein
Jul 28, 2009·PloS One·Yi ZhangJo Anne Powell-Coffman
Sep 29, 2009·Current Opinion in Cell Biology·Robert B Hamanaka, Navdeep S Chandel
Mar 26, 2010·Nature·Cynthia J Kenyon
Oct 23, 2010·Molecular Cell·Amar J MajmundarM Celeste Simon
Mar 4, 2011·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Vera P KrymskayaElena A Goncharova
May 31, 2011·Free Radical Biology & Medicine·Michael Ristow, Sebastian Schmeisser
Aug 13, 2011·The New England Journal of Medicine·Gregg L Semenza
Mar 23, 2012·Nature Reviews. Molecular Cell Biology·D Grahame HardieSimon A Hawley
Mar 27, 2012·Biochimica Et Biophysica Acta·Mark W PellegrinoCole M Haynes
Apr 17, 2012·Cell·Mathieu Laplante, David M Sabatini
May 9, 2012·Cell Metabolism·Stacey Robida-StubbsT Keith Blackwell
Feb 20, 2013·The Journals of Gerontology. Series A, Biological Sciences and Medical Sciences·Scott F LeiserMatt Kaeberlein
May 24, 2013·Nature·Riekelt H HoutkooperJohan Auwerx

Related Concepts

Calcinus elegans
Tetracycline Antibiotics
RHEBP1 gene
Metabolic Process, Cellular
Cyartonema elegans
Coleonyx elegans
Biochemical Pathway
Let-363 protein, C elegans

Related Feeds

Autophagy & Metabolism

Autophagy preserves the health of cells and tissues by replacing outdated and damaged cellular components with fresh ones. In starvation, it provides an internal source of nutrients for energy generation and, thus, survival. A powerful promoter of metabolic homeostasis at both the cellular and whole-animal level, autophagy prevents degenerative diseases. It does have a downside, however--cancer cells exploit it to survive in nutrient-poor tumors.

Autophagy & Model Organisms

Autophagy is a cellular process that allows degradation by the lysosome of cytoplasmic components such as proteins or organelles. Here is the latest research on autophagy & model organisms