RRC ID 45728
Author Folick A, Oakley HD, Yu Y, Armstrong EH, Kumari M, Sanor L, Moore DD, Ortlund EA, Zechner R, Wang MC.
Title Aging. Lysosomal signaling molecules regulate longevity in Caenorhabditis elegans.
Journal Science
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 in metazoans.
Volume 347(6217)
Pages 83-6
Published 2015-1-2
DOI 10.1126/science.1258857
PII 347/6217/83
PMID 25554789
PMC PMC4425353
MeSH Active Transport, Cell Nucleus Animals Caenorhabditis elegans / genetics Caenorhabditis elegans / physiology* Caenorhabditis elegans Proteins / genetics Caenorhabditis elegans Proteins / metabolism* Cell Nucleus / metabolism Lipase / metabolism Lipid Metabolism Longevity / genetics Longevity / physiology* Lysosomes / metabolism* Molecular Chaperones / genetics Molecular Chaperones / metabolism* Receptors, Cytoplasmic and Nuclear / metabolism Signal Transduction
IF 41.846
Times Cited 109
C.elegans tm4417 tm1011 tm3860