Lysosomal signaling molecules regulate longevity in Caenorhabditis elegans

• Persistent URL: No alternate ID available
• Type of Material: Article
• Authors: Andrew Folick, Baylor College of Medicine; Holly Doebbler Oakley, Baylor College of Medicine; Yong Yu, Baylor College of Medicine; Eric H. Armstrong, Emory University; Manju Kumari, University of Graz; Lucas Sanor, Baylor College of Medicine; David D. Moore, Baylor College of Medicine; Eric Ortlund, Emory University; Rudolf Zechner, University of Graz; Meng C. Wang, Baylor College of Medicine
• Language: English
• Date: 2015-01-02
• Publisher: AMER ASSOC ADVANCEMENT SCIENCE
• Publication Version: Author Accepted Manuscript (After Peer Review)
• Copyright Statement: American Association for the Advancement of Science
• Final Published Version (URL): http://dx.doi.org/10.1126/science.1258857
• Title of Journal or Parent Work: SCIENCE
• Volume: 347
• Issue: 6217
• Start Page: 83
• End Page: 86
• Grant/Funding Information: Supported by NIH grants T32GM008602 (E.H.A), RO1DK095750 (E.A.O), T32HD055200 (A.F.), F30AG046043 (A.F.), RO0AG034988 (M.C.W), RO1AG045183(M.C.W.); Ellison New Scholar Award (M.C.W.); ERC-Advanced grant (R.Z.); Fondation Leducq (R.Z.)
• Keywords: ACID-BINDING PROTEINS; Science & Technology - Other Topics; C-ELEGANS; METABOLISM; DIET; OLEOYLETHANOLAMIDE; RESTRICTION; Science & Technology; Multidisciplinary Sciences
• Research Categories: Biology, Genetics; Biology, Cell; Chemistry, Biochemistry

Abstract

Lysosomes are crucial cellular organelles for human health that function in digestion and recycling of extracellular and intracellular macromolecules.We describe a signaling role for lysosomes that affects aging. In the worm Caenorhabditis elegans, the lysosomal acid lipase LIPL-4 triggered nuclear translocalization of a lysosomal lipid chaperone LBP-8, which promoted longevity by activating the nuclear hormone receptors NHR-49 and NHR-80.We used high-throughput metabolomic analysis to identify several lipids in which abundance was increased in worms constitutively overexpressing LIPL-4. Among them, oleoylethanolamide directly bound to LBP-8 and NHR-80 proteins, activated transcription of target genes of NHR-49 and NHR-80, and promoted longevity in C. elegans.These findings reveal a lysosome-to-nucleus signaling pathway that promotes longevity and suggest a function of lysosomes as signaling organelles inmetazoans.