A new study combines metallomics and metabolomics to examine how disturbances in metal homeostasis reshape metabolic pathways in the model organism Caenorhabditis elegans. Researchers exposed C. elegans to acute and chronic doses of iron, manganese, or zinc to examine how shifts in metal availability affect cellular metabolism.
Using metal-free size-exclusion chromatography coupled to inductively coupled plasma mass spectrometry (SEC–ICP-MS), the team quantified how each metal redistributed between high-molecular-mass, low-molecular-mass, and inorganic pools. In parallel, Fourier transform ion cyclotron resonance mass spectrometry (FT-ICR-MS) was used to capture broad metabolomic changes associated with these perturbations.
Across experiments, zinc emerged as a central regulator of metal balance. Iron and manganese exposure consistently reduced total zinc levels, suggesting competitive interactions for shared binding sites and activation of zinc excretion pathways. Conversely, zinc treatment altered the distribution of both iron and manganese species, indicating that zinc availability influences how redox-active metals are buffered within the cell.
Metabolomic profiling showed that metal imbalance affected not only metal pools but also core metabolic pathways. Chronic iron exposure produced marked shifts in metabolites associated with central carbon metabolism, including accumulation of succinic acid and depletion of intermediates feeding acetyl-CoA production. These patterns are consistent with impaired energy metabolism and increased metabolic demand.
By comparison, manganese exposure resulted in subtler but distinct metabolic changes, while zinc treatment led to relatively modest disruption of metabolic profiles.
The researchers highlight that neurons, with their high energetic demands, may be particularly sensitive to metabolic strain arising from disrupted metal homeostasis – a vulnerability that could help explain links between metal imbalance and neurodegenerative processes.
While the findings are limited to C. elegans, the authors emphasize that combining metal speciation analysis with untargeted metabolomics provides a structured approach for examining metal–metabolism interactions. They suggest that extending similar workflows to other model systems could help clarify how metal dysregulation contributes to aging and neurodegeneration.
Newsletters
Receive the latest analytical science news, personalities, education, and career development – weekly to your inbox.
