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PMID: 12958363 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, P.H.S.

Autophagy genes are essential for dauer development and life-span extension in C. elegans.

Science (New York, N.Y.) ·Vol. 301 ·No. 5638 ·2003-09-05 ·Pages 1387-91

Meléndez A, Tallóczy Z, Seaman M, Eskelinen EL, Hall DH, Levine B

Abstract

Both dauer formation (a stage of developmental arrest) and adult life-span in Caenorhabditis elegans are negatively regulated by insulin-like signaling, but little is known about cellular pathways that mediate these processes. Autophagy, through the sequestration and delivery of cargo to the lysosomes, is the major route for degrading long-lived proteins and cytoplasmic organelles in eukaryotic cells. Using nematodes with a loss-of-function mutation in the insulin-like signaling pathway, we show that bec-1, the C. elegans ortholog of the yeast and mammalian autophagy gene APG6/VPS30/beclin1, is essential for normal dauer morphogenesis and life-span extension. Dauer formation is associated with increased autophagy and also requires C. elegans orthologs of the yeast autophagy genes APG1, APG7, APG8, and AUT10. Thus, autophagy is a cellular pathway essential for dauer development and life-span extension in C. elegans.

MeSH Terms
Animals Animals, Genetically Modified Apoptosis Regulatory Proteins Autophagy/genetics Beclin-1 Caenorhabditis elegans/genetics,growth & development,metabolism,ultrastructure Caenorhabditis elegans Proteins/chemistry,genetics,metabolism,physiology Genes, Fungal Genes, Helminth Humans Longevity Membrane Proteins Morphogenesis Mutation Phagosomes/ultrastructure Phenotype Proteins/chemistry,genetics,physiology RNA Interference Receptor, Insulin/genetics,metabolism Recombinant Fusion Proteins/metabolism Saccharomyces cerevisiae/genetics,physiology Signal Transduction Vesicular Transport Proteins
Chemicals
Apoptosis Regulatory Proteins BECN1 protein, human Beclin-1 Caenorhabditis elegans Proteins Membrane Proteins Proteins Recombinant Fusion Proteins Vesicular Transport Proteins bec-1 protein, C elegans DAF-2 protein, C elegans Receptor, Insulin
Authors & Affiliations
6 authors, click to expand affiliations / ORCID
Meléndez Alicia
Department of Medicine, Columbia University College of Physicians & Surgeons, 630 West 168th Street, New York, NY 10032, USA.
Tallóczy Zsolt
Seaman Matthew
Eskelinen Eeva-Liisa
Hall David H
Levine Beth
Article Info
Journal
Science (New York, N.Y.)
Abbr.
Science
ISSN
1095-9203
Published
2003-09-05
Pages
1387-91
Language
English
Region
United States
NLM ID
0404511
Subset
IM
Grants
NIH HHS · R24 OD010943 · United States
NCRR NIH HHS · R24 RR012596 · United States
NCI NIH HHS · CA84254 · United States
NCRR NIH HHS · RR 12596 · United States
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