| 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
|
|
WOS Category
|
MULTIDISCIPLINARY SCIENCES
|
| Resource |
| C.elegans |
tm4417
tm1011
tm3860 |
