Combined metallomics and metabolomics reveal impact of metal homeostasis on biological pathways in C. elegans

TL;DR

This study uses advanced techniques to show how metal imbalances affect metabolism in C. elegans, highlighting zinc's role and iron's impact on energy metabolism.

Contribution

The novel integration of metallomics and metabolomics reveals specific metal-metabolite interactions in C. elegans under metal homeostasis disruption.

Findings

Zinc regulates free iron and manganese species in metal homeostasis.

Iron exposure causes metabolomic changes indicating impaired energy metabolism.

Abstract

Trace metals and metal homeostasis play an essential role in cell metabolism, and an imbalance in this careful balance leads to pathological changes. In neurodegenerative diseases such as Parkinson’s disease, trace metals and metal species are increasingly recognized as key factors in disease progression in mechanisms such as ferroptosis. In this study, we combined modern analytical techniques like Fourier transform ion cyclotron resonance mass spectrometry (FT-ICR-MS) with metal-free high-pressure liquid chromatography inductively coupled plasma mass spectrometry (HPLC-ICP-MS) to analyze metabolomic and metallomic changes in the model organism Caenorhabditis elegans under conditions of induced metal homeostasis imbalance. Our results identified zinc as a key player in the regulation of free metal species of iron and manganese. Furthermore, iron exposure resulted in distinct metabolomic patterns indicative of impaired energy metabolism, suggesting an exhaustion of cellular metabolic energy capacity.

The online version contains supplementary material available at 10.1007/s00216-025-06306-z.

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