fndc-1 (C. elegans) research notes
UniProt: Q22252 (FNDC1_CAEEL) · WormBase: WBGene00011528 / locus T06D8.7 ·
mammalian ortholog: FUNDC1 · Family: FUN14 (Pfam PF04930, InterPro IPR007014).
Naming note: the task/flagship project refers to this gene as "fundc-1" (after
mammalian FUNDC1). The official WormBase symbol is fndc-1 (used by UniProt with
ECO:0000303|PubMed:31233739 and ECO:0000312|WormBase:T06D8.7). All work here uses the
correct WormBase symbol fndc-1. The earlier project note ("no clear C. elegans
ortholog in UniProt") reflects a symbol mismatch, not a missing gene — Q22252 is a
reviewed Swiss-Prot entry.
Protein / identity (established)
- 138-aa integral membrane protein with two predicted TM helices (residues 37–56,
61–78; ECO:0000255) and UniProt subcellular location "Mitochondrion outer membrane …
Multi-pass membrane protein" (ECO:0000305|PubMed:31233739). Small multi-pass OMM
topology is the hallmark of the FUN14/FUNDC1 family.
- Sole informative domain: FUN14 (the FUNDC1 family fold). No enzymatic domain — this is
an adaptor/receptor-type protein, not an enzyme.
What is KNOWN in C. elegans (peer-reviewed, worm-established)
- Contributes to paternal-mitochondria elimination after fertilization.
- PMID:31233739
- PMID:31233739
- Functional read-out that paternal mtDNA persists without fndc-1:
PMID:31233739
- The authors frame this as the first ubiquitin-independent mitophagy receptor for
sperm-mitochondria degradation:
PMID:31233739
- fndc-1 is a second, temporally distinct route, redundant with an earlier
ubiquitin-dependent (ubc-18/ubc-16 → proteasome/LGG-1) mechanism:
PMID:31153831
PMID:31153831
-
The phenotype is a delay, not a block (redundancy) → mild loss-of-function.
-
Mediates hypoxia-reoxygenation (HR)-induced mitophagy in somatic tissue (body-wall muscle).
- Establishes the worm ortholog identity explicitly:
PMID:33416042
- Protection on loss depends on the UPRmt transcription factor ATFS-1:
PMID:33416042
- FNDC-1 also has a role in non-hypoxic (basal) mitochondrial quality control:
PMID:33416042
-
(Quantitative HR-mitophagy data — mito-mKeima, mRuby3::FNDC-1 co-localization,
proteinase-K OMM topology — are in the Lim 2021 full text, not the cached abstract.)
-
Localization: mitochondrial outer membrane.
- UniProt curated from primary lit (PubMed:31233739); GOA carries IBA (GO_REF:0000033)
and IEA (GO_REF:0000044, UniProt-SubCell) OMM annotations. TM topology + FUN14 family
are consistent. Established.
What is INFERRED from mammalian FUNDC1 (NOT directly shown in worm)
- LC3-interacting region (LIR) motif and direct ATG8 binding. Mammalian FUNDC1 uses a
phospho-regulated LIR to bind LC3/GABARAP. In worm, no LIR has been mapped/mutated and
no direct FNDC-1–LGG-1/LGG-2 (ATG8) interaction has been demonstrated. The
"receptor/adaptor" molecular activity in worm rests on genetic loss-of-function +
orthology, i.e. it is an ISS-level MF claim, not a direct assay.
- Phospho/ubiquitin regulation (SRC, CK2, ULK1, PGAM5, MARCH5 acting on the LIR in
mammals) — none demonstrated for worm FNDC-1.
- MAM enrichment / DRP-1 recruitment / oocyte-to-zygote-transition (MOZT) developmental
mitophagy. These appear only in 2025 preprints (bioRxiv 2025.02.01.636045;
Research Square rs.3.rs-6330979) — treated here as preliminary and deliberately kept out
of the top-level description and out of any peer-reviewed annotation. Documented as an
open/narrowing knowledge gap only.
Existing GOA annotations (6) and disposition
| GO term |
Aspect |
Evidence |
Ref |
Action |
| GO:0000422 autophagy of mitochondrion |
BP |
IBA |
GO_REF:0000033 |
ACCEPT |
| GO:0005741 mitochondrial outer membrane |
CC |
IBA |
GO_REF:0000033 |
ACCEPT |
| GO:0005741 mitochondrial outer membrane |
CC |
IEA |
GO_REF:0000044 |
ACCEPT |
| GO:0006914 autophagy |
BP |
IEA |
GO_REF:0000043 |
ACCEPT (general parent; subsumed by mitophagy terms) |
| GO:0000423 mitophagy |
BP |
IMP |
PMID:31153831 |
ACCEPT |
| GO:0000423 mitophagy |
BP |
IMP |
PMID:31233739 |
ACCEPT |
Proposed NEW (not in GOA):
- GO:0140580 mitochondrion autophagosome adaptor activity — the missing MF term.
Coded ISS (not IDA): the adaptor/bridging activity is inferred from mammalian FUNDC1
orthology + worm genetic phenotype; direct LGG-1/LGG-2 binding is not shown in worm.
- GO:0071456 cellular response to hypoxia — IMP from Lim 2021 HR model
(fndc-1 loss changes HR outcome). Worm-established.
Knowledge gaps (see YAML knowledge_gaps)
- Molecular adaptor mechanism / LIR + LGG-1/LGG-2 partner not experimentally established in worm.
- Regulation of FNDC-1 (post-translational switches) uncharacterized in worm.
- Physiological scope / pathway placement (vs PINK-1/PDR-1, DCT-1/NIX) unresolved; phenotype
mild/context-restricted; some stresses (acute heat) remodel mitochondria independently of fndc-1.
Explicit field admission (deep-research synthesis, grep-verified in the falcon report):
"Direct phosphorylation/ubiquitination mapping and LIR validation for C. elegans FNDC-1
remain to be fully elucidated."
Provenance / sources
- Cached abstracts (abstract-only,
full_text_available: false):
publications/PMID_31233739.md, PMID_31153831.md, PMID_33416042.md.
- Deep research: genes/worm/fndc-1/fndc-1-deep-research-falcon.md (Edison Scientific,
real run, 27 citations). Review/preprint claims (Ganguly 2024; Choubey 2021; Liu 2020;
Haeussler 2020; Thendral/Sherwood 2025 preprints) used only for context/inference, not
for peer-reviewed annotation.