# Molecular mechanisms of CYP-13 function in C. elegans: insights into conserved P450 pathways

**Authors:** Sharoen Yu Ming Lim

PMC · DOI: 10.1007/s00204-025-04284-w · 2026-01-14

## TL;DR

This paper explores the diverse roles of CYP-13 in C. elegans, linking it to lifespan, stress, and metabolism with implications for human health.

## Contribution

It reveals CYP-13 as a multifunctional hub connecting development, apoptosis, and metabolism in C. elegans.

## Key findings

- CYP-13 integrates with DAF-16/FOXO and HSF-1 pathways to regulate lifespan.
- CYP-13 contributes to apoptosis via the degradosome complex with CPS-6/EndoG and WAH-1.
- CYP-13A12 regulates reoxygenation responses through the EGL-9–HIF-1–PUFA pathway.

## Abstract

Cytochrome P450 enzymes (CYPs) are central to metabolism and stress adaptation. In Caenorhabditis elegans, the CYP-13 family performs diverse and conserved functions beyond xenobiotic detoxification. cyp-13 links lifespan regulation to the APP ortholog apl-1 and the heterochronic factor lin-14, integrating with DAF-16/FOXO, HSF-1, and DAF-12 pathways. In apoptosis, cyp-13 contributes to the degradosome complex with CPS-6/EndoG and WAH-1, facilitating DNA degradation. Several isoforms are inducible by aflatoxin B1 and PCB1254, underscoring roles in toxicant metabolism. Notably, cyp-13A12 regulates behavioral responses to reoxygenation via the EGL-9–HIF-1–PUFA–eicosanoid pathway, paralleling mammalian ischemia–reperfusion responses. Epigenetic regulation adds another layer, as BRCA1/BARD1 homologs brc-1 and brd-1 repress distinct subsets of cyp-13A genes through H2A ubiquitylation. Collectively, CYP-13 emerges as a multifunctional hub linking developmental, apoptotic, metabolic, stress, and chromatin-level processes, with clear parallels to human CYPs, highlighting its translational relevance to aging, cancer, and toxicology.

## Linked entities

- **Genes:** CYP13 (putative cyclophilin 13) [NCBI Gene 5068010], ADI1 (acireductone dioxygenase 1) [NCBI Gene 55256], lin-14 (Protein lin-14) [NCBI Gene 181337], daf-16 (Forkhead box protein O) [NCBI Gene 172981], HSF1 (heat shock transcription factor 1) [NCBI Gene 3297], daf-12 (Nuclear hormone receptor HR3;Nuclear hormone receptor family member daf-12) [NCBI Gene 181263], cps-6 (Endonuclease G, mitochondrial) [NCBI Gene 172045], wah-1 (Pyr_redox_2 domain-containing protein) [NCBI Gene 176635], egl-9 (Hypoxia-inducible factor prolyl hydroxylase) [NCBI Gene 179461], HIF1A (hypoxia inducible factor 1 subunit alpha) [NCBI Gene 3091], brc-1 (Breast cancer type 1 susceptibility protein homolog;RING-type E3 ubiquitin transferase BRCA1) [NCBI Gene 175499], BRD1 (bromodomain containing 1) [NCBI Gene 23774], H2AC18 (H2A clustered histone 18) [NCBI Gene 8337]
- **Proteins:** CYP13 (putative cyclophilin 13), APP (amyloid beta precursor protein), HSF1 (heat shock transcription factor 1), daf-12 (Nuclear hormone receptor HR3;Nuclear hormone receptor family member daf-12), wah-1 (Pyr_redox_2 domain-containing protein), egl-9 (Hypoxia-inducible factor prolyl hydroxylase), HIF1A (hypoxia inducible factor 1 subunit alpha), brc-1 (Breast cancer type 1 susceptibility protein homolog;RING-type E3 ubiquitin transferase BRCA1), BRD1 (bromodomain containing 1)
- **Chemicals:** aflatoxin B1 (PubChem CID 186907), PCB1254 (PubChem CID 40470)
- **Species:** Caenorhabditis elegans (taxon 6239)

## Full-text entities

- **Genes:** ADI1 (acireductone dioxygenase 1) [NCBI Gene 55256] {aka APL1, ARD, ARD', Fe-ARD, HMFT1638, MTCBP1}, HSF1 (heat shock transcription factor 1) [NCBI Gene 3297] {aka HSTF1}, H2AC18 (H2A clustered histone 18) [NCBI Gene 8337] {aka H2A, H2A.2, H2A/O, H2A/q, H2AFO, H2a-615}, ENDOG (endonuclease G) [NCBI Gene 2021], HIF1A (hypoxia inducible factor 1 subunit alpha) [NCBI Gene 3091] {aka HIF-1-alpha, HIF-1A, HIF-1alpha, HIF1, HIF1-ALPHA, MOP1}, BRD1 (bromodomain containing 1) [NCBI Gene 23774] {aka BRL, BRPF2}, BRCA1 (BRCA1 DNA repair associated) [NCBI Gene 672] {aka BRCAI, BRCC1, BROVCA1, FANCS, IRIS, PNCA4}, BARD1 (BRCA1 associated RING domain 1) [NCBI Gene 580], APP (amyloid beta precursor protein) [NCBI Gene 351] {aka AAA, ABETA, ABPP, AD1, APPI, CTFgamma}
- **Diseases:** ischemia (MESH:D007511), cancer (MESH:D009369)
- **Chemicals:** PUFA (MESH:D005231), eicosanoid (MESH:D015777), aflatoxin B1 (MESH:D016604), PCB1254 (-)
- **Species:** Caenorhabditis elegans (species) [taxon 6239], Homo sapiens (human, species) [taxon 9606], C. elegans [taxon 328850]

## Figures

2 figures with captions in the complete paper: https://tomesphere.com/paper/PMC13043600/full.md

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Source: https://tomesphere.com/paper/PMC13043600