Aging. Lysosomal signaling molecules regulate longevity in Caenorhabditis elegans
| Autor: | Folick, Andrew, Oakley, Holly D, Yu, Yong, Armstrong, Eric H, Kumari, Manju, Sanor, Lucas, Moore, David D, Ortlund, Eric A, Zechner, Rudolf, Wang, Meng C |
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| Rok vydání: | 2015 |
| Předmět: |
Cell Nucleus
Aging Cytoplasmic and Nuclear General Science & Technology 1.1 Normal biological development and functioning Longevity Lipase Lipid Metabolism Active Transport Underpinning research Receptors Genetics Animals Generic health relevance Lysosomes Caenorhabditis elegans Caenorhabditis elegans Proteins Molecular Chaperones Signal Transduction |
| Zdroj: | Science (New York, N.Y.), vol 347, iss 6217 |
| Popis: | 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 in metazoans. |
| Databáze: | OpenAIRE |
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