The molecular landscape of cellular metal ion biology

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Simran Aulakh Oliver Lemke Lukasz Szyrwiel Stephan Kamrad Yu Chen Johannes Hartl Michael Mülleder Jens Nielsen Markus Ralser
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Abstract

Metal ions have crucial roles in cells, but the impact of their availability on biological networks is underexplored. We systematically quantified yeast cell growth and the corresponding metallomic, proteomic, and genetic responses to perturbations in metal availability along concentration gradients of all growth-essential metal ions. We report a remarkable metal concentration dependency of cellular networks, with around half of the proteome, and most signaling pathways such as target of rapamycin (TOR), being metal responsive. Although the biological response to each metal is distinct, our data reveal common properties of metal responsiveness, such as concentration interdependencies and metal homeostasis. Furthermore, our resource indicates that many understudied proteins have functions related to metal biology and reveals that metalloenzymes occupy central nodes in metabolic networks. This work provides a framework for understanding the critical role of metal ions in cellular function, with broader implications for manipulating metal homeostasis in biotechnology and medicine.

Journal details

Journal Cell systems
Volume 16
Issue number 7
Pages 101319
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Publisher website (DOI) 10.1016/j.cels.2025.101319
Europe PubMed Central 40516524
Pubmed 40516524

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The publication was previously a preprint. View preprint

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