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<p>Cytochrome P450 enzymes (CYPs) are central to metabolism and stress adaptation. In <i>Caenorhabditis elegans</i>, the CYP-13 family performs diverse and conserved functions beyond xenobiotic detoxification. <i>cyp-13</i> links lifespan regulation to the APP ortholog <i>apl-1</i> and the heterochronic factor <i>lin-14</i>, integrating with DAF-16/FOXO, HSF-1, and DAF-12 pathways. In apoptosis, <i>cyp-13</i> 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, <i>cyp-13A12</i> 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 <i>brc-1</i> and <i>brd-1</i> repress distinct subsets of <i>cyp-13A</i> 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.</p>

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

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  • 发表日期：

    2026年1月14日

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  • Sharoen Yu Ming Lim

摘要

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.