It is well established that differentmetalloproteins and metalloenzymes localize to different
cellular compartments, for example, zinc-dependent polymerases
in the nucleus, iron−sulfur cluster biogenesis
machinery in mitochondria, and manganese-dependent photosystem
II in the thylakoid membrane of chloroplasts. Just as
different cells and organisms have different metal requirements,
2 so too will compartments within cells. In fact, even in
cells with minimal compartmentalization such as bacteria,
differences between metal availability in the cytosol and
periplasm may play a critical role in ensuring proper metalation
of proteins. In a proof of principle study, Robinson and coworkers
demonstrated that the compartment in which a protein
folds can determine which metal is bound to the protein,
suggesting that one important feature of compartmentalization
is to segregate metals to ensure that the right proteins have
access to the right metals.63 One of the exciting applications of
fluorescent metal sensors is the potential to visualize and
quantify the accessible metal pool in the cytoplasm as well as in
distinct compartments