Metals in Cells: Control of Cellular Metal Concentration

Abstract There are arrays of intricate systems for controlling the cellular metal economy, that is, the sum of import, sensing, utilization, storage, and export processes that keeps the transition metal quota or “metallome” of the cell in the optimal position for survival in a given environment. The cellular metallome corresponds to the amount of both uncoordinated “free” and complexed transition metal ions for a given organism. Over the past several years, it has become apparent that selective complexation by receptors and active compartmentalization are key to the cellular management of each metal. Long thought to be present only at “trace” levels in biology, transition metals are hardly trace from a cellular point of view. Many cells accumulate metals such as zinc and iron to concentrations approaching millimolar levels and then maintain this concentration within a narrow range. This raises the question, how cells maintain tight regulation of the metal ion quotas while avoiding the toxicity of extra free ions in the cell? This article and the many others in this book introduce a few of the chemical considerations, the metal receptors and the metal‐trafficking proteins that regulate the intracellular metallome.