Lysosome-to-nucleus lipid signalling in C. elegans

Reviewing GO annotations for the four genes of the OEA longevity pathway

AI Gene Review · projects/CAEEL_LYSOSOME_NUCLEUS_LIPID_SIGNALING · 2026

Bottom line

  • LIPL-4 releases OEA in the lysosome, LBP-8 carries it to the nucleus, and NHR-80 with NHR-49 turns on lipid genes that extend lifespan (PMID:25554789).
  • All four genes reviewed: 74 rows, 60 ACCEPT, 6 MODIFY, 4 NEW.
  • Corrections make the signal explicit: LBP-8 gets lipid transfer activity in place of a transmembrane transporter term, ligand-modulated TF activity for NHR-80. Downstream targets are not yet reviewed.

The pathway

Why this pathway

  • Short and well characterised: one enzyme, one chaperone, one receptor pair.
  • A direct binding measurement: NHR-80 binds OEA with Kd about 7.8 µM.
  • Needed for germline-loss (glp-1) longevity, separable from insulin/IGF and dietary restriction.
  • Test: can GO terms express a lipid messenger moving from lysosome to nucleus?

A MODIFY in practice

nhr-80: the IEA DNA-binding transcription factor row is modified to ligand-modulated transcription factor activity or nuclear receptor activity.

Results per gene

Gene Role Rows ACCEPT Non-core Over-ann. MODIFY NEW
lipl-4 lysosomal acid lipase 14 13 1 0 0 0
lbp-8 FABP lipid chaperone 17 15 0 0 1 1
nhr-80 OEA receptor 15 10 2 0 1 2
nhr-49 NHR-80 partner 28 22 0 1 4 1

No REMOVE actions. NEW: intracellular lipid transport (lbp-8), ligand-modulated TF activity and nuclear receptor binding (nhr-80), cellular response to hypoxia (nhr-49).

Status and next steps

  • ✅ lipl-4, lbp-8, nhr-80, nhr-49 reviewed.
  • ⬜ Review downstream targets fat-5, fat-6, fat-7, acs-2 and the glp-1 longevity context.
  • Related reviews already in the repo: hlh-30 (TFEB, regulates lipl-4) and daf-16.

Read more: projects/CAEEL_LYSOSOME_NUCLEUS_LIPID_SIGNALING.md · genes/worm/<gene>/