Authors: MelÃ©ndez A; TallÃ³czy 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.Keywords: Animals; Animals, Genetically Modified; Apoptosis Regulatory Proteins; Autophagy/*genetics; 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
Journal: Science (New York, N.Y.)
Date: Sept. 6, 2003
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MelÃ©ndez A, TallÃ³czy Z, Seaman M, Eskelinen EL, Hall DH, Levine B (2003) Autophagy genes are essential for dauer development and life-span extension in C. elegans. Science (New York, N.Y.) 301: 1387-91.