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

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.