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

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.

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.

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