Objective:

To examine how disturbances in metal homeostasis reshape metabolic pathways in Caenorhabditis elegans.

Key Findings:

• Zinc is a central regulator of metal balance, with iron and manganese exposure reducing total zinc levels.
• Zinc treatment alters the distribution of iron and manganese species within cells.
• Chronic iron exposure leads to significant shifts in metabolites linked to central carbon metabolism, indicating impaired energy metabolism.
• Manganese exposure causes subtler metabolic changes, while zinc treatment results in modest disruptions.

Interpretation:

Neurons may be particularly sensitive to metabolic strain from disrupted metal homeostasis, potentially linking metal imbalance to neurodegenerative processes.

Limitations:

• Findings are limited to the model organism C. elegans.
• Further research is needed to extend these findings to other systems.

Conclusion:

Combining metal speciation analysis with untargeted metabolomics offers a structured approach to studying metal–metabolism interactions, with implications for understanding aging and neurodegeneration.