Autophagy Genes Are Essential for Dauer Development and Life-Span Extension in C. elegans
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.
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We thank J. Yu, W. Jiang, F. Macaluso, and G. Stephney for excellent technical assistance; R. Chamberlain for secretarial assistance; A. Fire, Y. Kohara, and T. Stiernagle for providing reagents; and H. Bülow for helpful discussions. We are particularly grateful to I. Greenwald for generous support. Supported by NIH grant nos. RO1 CA84254 (B.L. and A.M.) and RR 12596 (D.H.H.), American Cancer Society grant no. RSG-339 (B.L), and the Medical Research Council of the UK (M.S.).
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Published In
Science
Volume 301 | Issue 5638
5 September 2003
5 September 2003
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American Association for the Advancement of Science.
Submission history
Received: 9 June 2003
Accepted: 28 July 2003
Published in print: 5 September 2003
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www.sciencemag.org/cgi/content/full/301/5638/1387/DC1
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Fig. S1
Table S1
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- Alicia Meléndez et al.
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