Genetically encoded fluorescent sensor for intracellular imaging of transition metals

Transition metals possess a paradoxical role in living organisms. While acting as indispensable cofactors for proteins, transition metals at elevated levels lead to protein dysfunction or inactivation, disease, or even death. The tracing of transition metals in living cells offers a better understanding of intracellular transition metal homeostasis and related diseases. Genetically encoded fluorescent sensors are attractive approaches for intracellular transition metal imaging and monitoring, due to their intrinsic advantages, including noninvasive and subcellular localization. Recent studies have achieved fruitful progress for intracellular imaging of zinc and copper using genetically encoded fluorescent sensors, yet challenges still remain. In this review we present a general view on the intracellular transition metal homeostasis and basic concepts on genetically encoded fluorescent sensors and focus on the recent developments in genetically encoded fluorescent sensors for transition metals, especially zinc and copper. Future perspectives in this field are also discussed.