Kelly Deng, Christopher J Chang
Transition metals are essential nutrients that serve as metabolic cofactors and signaling agents in every cell type across all kingdoms of life. Owing to their relatively low abundance and high chemical reactivity, living organisms have evolved dedicated biochemical pathways to ensure active acquisition and targeted delivery of transition metals to their proper locations across biological length scales spanning tissues to cells to proteins, thus promoting beneficial physiology and avoiding detrimental pathology. Here we summarize recent advances in the discovery of copper metalloadaptor and zinc metallochaperone proteins that reveal new foundational chemical principles of biological metal homeostasis.