The molecular landscape of cellular metal ion biology
Open accessPublished version of a preprint
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.
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- Authors
- Aulakh, S. K., Lemke, O., Szyrwiel, L., Kamrad, S., Chen, Y., Hartl, J., Mülleder, M., Nielsen, J., & Ralser, M.
- Affiliations
- Centre for Human Genetics (GB)
- Berlin Institute of Health at Charité - Universitätsmedizin Berlin (DE)
- The Francis Crick Institute (GB)
- Chinese Academy of Sciences (CN)
- Charité – Universitätsmedizin Berlin (DE)
- BioInnovation Institute (DK)
- Corresponding author
- Ralser, Markus
- ORCID
- Venue
- Cell Systems
- Publisher
- Elsevier BV
- Published
- 2025-07
- Volume
- 16
- Issue
- 7
- Pages
- 101319
- ISSN
- 2405-4712 (ISSN-L)
- OpenAlex
- W4411257028
- Cited by
- 19
- References
- 9
- Citations by year
- 2026: 13 · 2025: 4 · 2024: 2
- FWCI
- 5.11
- Type
- journal article
- Language
- en
- Update notices
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Cell Systems (publishedVersion, cc-by-nc-nd)
- bioRxiv (Cold Spring Harbor Laboratory) (acceptedVersion, cc-by-nc)
- PubMed (publishedVersion)
- Chalmers Research (Chalmers University of Technology) (submittedVersion)
- Funders
- Wellcome Trust (FC001134, IA 200829/Z/16/Z)
- European Research Council (951475)
- UK Research and Innovation Medical Research Council
- The Francis Crick Institute
- Cancer Research UK
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Fungal and yeast genetics research
- Health Sciences › Nursing › Nutrition and Dietetics › Trace Elements in Health
- Physical Sciences › Environmental Science › Health, Toxicology and Mutagenesis › Heavy Metal Exposure and Toxicity
- Keywords
- metal ions, metal homeostasis, metal availability, yeast growth, metallomics, TOR signaling, metalloenzymes, metabolic networks, proteomics
- MeSH terms
- Homeostasis, Ions, Metals, Saccharomyces cerevisiae, Signal Transduction, Proteome, Saccharomyces cerevisiae Proteins, Proteomics, Metabolic Networks and Pathways
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