Optical Recording of Zn2+ Dynamics in the Mitochondrial Matrix and Intermembrane Space with the GZnP2 Sensor
Zinc ion, Mitochondrial matrix, Intermembrane space, Fluorescent sensor GZnP1
The zinc ion (Zn2+) is emerging as an important signaling molecule. Here, we engineered an improved Zn2+ probe GZnP2 based on a previously developed fluorescent sensor GZnP1 to provide a higher fluorescent readout (2-fold higher) that is proportional to cellular labile Zn2+ concentrations. We further developed a set of GZnP2 derived imaging tools to determine the labile Zn2+ concentrations in the mitochondrial matrix, mitochondrial intermembrane space (IMS), and cytosol in four different cell lines (HeLa, Cos-7, HEK293, and INS-1). The labile Zn2+ concentration in the matrix was less than 1 pM, while the labile Zn2+ concentration in the IMS was comparable to the cytosol (∼100 pM). With these sensors, we showed that upon exposure to high Zn2+, only the cytosol and the IMS were overloaded with Zn2+, while the mitochondrial matrix was unable to sequester excess labile Zn2+ in depolarized INS-1 cells. This work highlighted the importance of distinguishing the labile Zn2+ concentrations and dynamics between the mitochondrial matrix and IMS.
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Fudge, Dylan H, et al. “Optical Recording of Zn2 Dynamics in the Mitochondrial Matrix and Intermembrane Space with the GZnP2 Sensor.” ACS Chemical Biology, vol. 13, no. 7, 2018, pp. 1897–1905. doi: 10.1021/acschembio.8b00319.