The molecular landscape of cellular metal ion biology
Journal article, 2025
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.
calcium poorly characterized proteins
zinc
metal signaling
copper
iron
metal responsiveness
metabolism
metal ion biology
gene function prediction
Author
Simran Kaur Aulakh
University of Oxford
The Francis Crick Institute
Oliver Lemke
Charité University Medicine Berlin
Berliner Institut für Gesundheitsforschung
Lukasz Szyrwiel
Charité University Medicine Berlin
Stephan Kamrad
The Francis Crick Institute
Yu Chen
Chalmers, Life Sciences, Systems and Synthetic Biology
Shenzhen Institute of Advanced Technology
Johannes Hartl
Charité University Medicine Berlin
Berliner Institut für Gesundheitsforschung
Michael Mülleder
Charité University Medicine Berlin
Jens B Nielsen
Chalmers, Life Sciences, Systems and Synthetic Biology
BioInnovation Institute
M. Ralser
Max Planck Society
Charité University Medicine Berlin
Berliner Institut für Gesundheitsforschung
University of Oxford
The Francis Crick Institute
Cell Systems
24054712 (ISSN) 24054720 (eISSN)
Vol. 16 7 101319Subject Categories (SSIF 2025)
Molecular Biology
DOI
10.1016/j.cels.2025.101319
PubMed
40516524