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.
metal responsiveness
gene function prediction
metal signaling
metal ion biology
calcium poorly characterized proteins
iron
metabolism
copper
zinc
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
Shenzhen Institute of Advanced Technology
Chalmers, Life Sciences, Systems and Synthetic Biology
Johannes Hartl
Charité University Medicine Berlin
Berliner Institut für Gesundheitsforschung
Michael Mülleder
Charité University Medicine Berlin
Jens B Nielsen
BioInnovation Institute
Chalmers, Life Sciences, Systems and Synthetic Biology
M. Ralser
Charité University Medicine Berlin
The Francis Crick Institute
University of Oxford
Berliner Institut für Gesundheitsforschung
Max Planck Society
Cell Systems
24054712 (ISSN) 24054720 (eISSN)
Vol. In Press 101319Subject Categories (SSIF 2025)
Molecular Biology
DOI
10.1016/j.cels.2025.101319