# A C. elegans model of copper deficiency: Dietary interventions rescue CTR1/CHCA-1 copper transporter mutant phenotype

## TL;DR

Researchers used C. elegans to model copper deficiency caused by a gene mutation and found that dietary changes can rescue the condition.

## Contribution

Established C. elegans as a model for copper deficiency and demonstrated dietary interventions can rescue mutant phenotypes.

## Key findings

- chca-1 mutant worms showed severe developmental defects on HT115 diet due to copper deficiency.
- Switching to OP50 diet or adding GSSG rescued the mutant phenotype and restored gene expression.
- Dietary interventions upregulated copper transporters, suggesting therapeutic potential for human disorders.

## Abstract

Copper is an essential micronutrient for all living organisms. Mutations in the copper-importing transporter CTR1/CHCA-1 are associated with a severe copper deficiency disorder in humans, for which no effective cures are currently available. Here, we develop C. elegans as a model for copper deficiency. We show that chca-1 mutant worms fed HT115 bacterial diet exhibited a severe developmental phenotype resulting from copper deficiency, reminiscent of the symptoms observed in human patients. Remarkably, this phenotype can be rescued by switching to OP50 bacterial diet or by supplementing HT115 bacterial diet with glutathione disulfide (GSSG), a metabolite enriched in OP50. Such dietary interventions remodeled the transcriptome of chca-1 mutants towards that of wild-type worms and upregulated the expression of CTR1/CHCA-1-like copper transporters, thereby ameliorating the mutant phenotype. Our findings establish C. elegans as a model for copper deficiency caused by CTR1/CHCA-1, suggesting that dietary interventions may offer a potential therapeutic approach for this severe disease.

Copper is an essential micronutrient for all living organisms. Mutations in the copper transporter CTR1 are associated with severe copper deficiency disorders in humans, for which no effective therapies currently exist. In this study, we established the nematode C. elegans as a model for copper deficiency. We found that worms with mutations in chca-1, the worm ortholog of human CTR1, exhibit severe developmental delay when fed HT115 bacteria, a phenotype resulting from copper deficiency. This developmental defect can be rescued by either switching the bacterial diet to OP50 or by supplementing HT115 with glutathione disulfide (GSSG), a metabolite naturally enriched in OP50 bacteria. These dietary interventions restore normal gene expression patterns and upregulate compensatory copper transporters in the mutant worms. Our findings identify dietary interventions as potential therapeutic strategies for copper deficiency disorders caused by defects in copper transport.