Mitophagy in C. elegans

Reviewing GO annotations for 17 genes of mitochondrial quality control

AI Gene Review · projects/CAEEL_MITOPHAGY · 2026

Bottom line

  • PINK-1, PDR-1 (Parkin) and the DCT-1 receptor mark damaged mitochondria for LGG-1/LGG-2 autophagy; ATFS-1 chooses repair (UPRmt) or removal.
  • We reviewed every GO annotation on 17 genes: 543 rows, 408 ACCEPT, 26 MODIFY, 3 REMOVE, 23 NEW.
  • Main outputs: a NEW mitophagy receptor function for DCT-1, specific terms replacing protein binding, and new transport and fission terms for MIRO-1.

Why mitophagy in the worm

  • PINK1 and Parkin were found through Parkinson's disease genetics; both are conserved in the worm.
  • The worm links mitochondrial quality control to lifespan (daf-2, hlh-30, skn-1).
  • Worm annotations feed orthology-based inference for the human pathway.
  • Three review tiers: core mitophagy and dynamics (6), autophagy machinery (6), regulators (5).

The pathway and the 17 genes

Actions per gene

What a review looks like

dct-1: the ancestral BNIP3-family cell-death row is kept as non-core; mitochondrial outer membrane is accepted.

Typical changes

Gene Existing term Action Proposed
dct-1 (none) NEW mitochondrion autophagosome adaptor activity (IDA)
pdr-1 autophagy (IEA) MODIFY mitophagy
sqst-1 protein binding (IPI) MODIFY autophagy cargo adaptor activity
lgg-1 GABA receptor binding (IBA) REMOVE none
skn-1 regulation of translation (IEA) REMOVE none
epg-5 neg. reg. of autophagosome assembly (IMP) MODIFY autophagosome maturation; autophagosome-lysosome fusion

All rows verified in genes/worm/<gene>/<gene>-ai-review.yaml.

Findings

  1. DCT-1 is the receptor: GO:0140580 proposed from direct evidence; its BNIP3-family cell-death role kept as non-core.
  2. LGG-1 acts upstream of LGG-2 in worms; LGG-2 tethers to HOPS for lysosome fusion.
  3. spg-7 is AFG3L2-like, not the human SPG7 ortholog (that is ppgn-1).
  4. Dynamin-family microtubule rows on DRP-1 and EAT-3: over-annotated or undecided after a 2026 re-review, not removed.

Status and next steps

  • ✅ 17/17 gene reviews and the pathway summary.
  • ⬜ Status notes on the project page (Dec 2025) predate the 2026 re-review; the BLUF gives current counts.
  • ⬜ fndc-1 (Q22252, FUNDC1 ortholog; genes/worm/fndc-1/): reviewed separately, also proposes GO:0140580; not yet counted in these totals.
  • ⬜ Six genes are shared with the proteostasis and UPR projects; do not sum totals across projects.

Read more: projects/CAEEL_MITOPHAGY.md · projects/CAEEL_MITOPHAGY/CAEEL_MITOPHAGY-pathway.md · genes/worm/<gene>/