Medizinische Universität Graz Austria/Österreich - Forschungsportal - Medical University of Graz
Gewählte Publikation:
SHR Neuro Krebs Kardio Lipid Stoffw Microb
Pak, VV; Ezeriņa, D; Lyublinskaya, OG; Pedre, B; Tyurin-Kuzmin, PA; Mishina, NM; Thauvin, M; Young, D; Wahni, K; Martínez Gache, SA; Demidovich, AD; Ermakova, YG; Maslova, YD; Shokhina, AG; Eroglu, E; Bilan, DS; Bogeski, I; Michel, T; Vriz, S; Messens, J; Belousov, VV.
Ultrasensitive Genetically Encoded Indicator for Hydrogen Peroxide Identifies Roles for the Oxidant in Cell Migration and Mitochondrial Function.
Cell Metab. 2020; 31(3):642-653
Doi: 10.1016/j.cmet.2020.02.003
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- Abstract:
- Hydrogen peroxide (H2O2) is a key redox intermediate generated within cells. Existing probes for H2O2 have not solved the problem of detection of the ultra-low concentrations of the oxidant: these reporters are not sensitive enough, or pH-dependent, or insufficiently bright, or not functional in mammalian cells, or have poor dynamic range. Here we present HyPer7, the first bright, pH-stable, ultrafast, and ultrasensitive ratiometric H2O2 probe. HyPer7 is fully functional in mammalian cells and in other higher eukaryotes. The probe consists of a circularly permuted GFP integrated into the ultrasensitive OxyR domain from Neisseria meningitidis. Using HyPer7, we were able to uncover the details of H2O2 diffusion from the mitochondrial matrix, to find a functional output of H2O2 gradients in polarized cells, and to prove the existence of H2O2 gradients in wounded tissue in vivo. Overall, HyPer7 is a probe of choice for real-time H2O2 imaging in various biological contexts. Copyright © 2020 Elsevier Inc. All rights reserved.