| Literature DB >> 32130885 |
Valeriy V Pak1, Daria Ezeriņa2, Olga G Lyublinskaya3, Brandán Pedre2, Pyotr A Tyurin-Kuzmin4, Natalie M Mishina5, Marion Thauvin6, David Young2, Khadija Wahni2, Santiago Agustín Martínez Gache2, Alexandra D Demidovich5, Yulia G Ermakova7, Yulia D Maslova5, Arina G Shokhina5, Emrah Eroglu8, Dmitry S Bilan9, Ivan Bogeski10, Thomas Michel8, Sophie Vriz11, Joris Messens2, Vsevolod V Belousov12.
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.Entities:
Keywords: D-amino acid oxidase; H(2)O(2); H(2)O(2) gradients; HyPer7; cell migration; chemogenetics; genetically encoded probes; hydrogen peroxide; mitochondria; redox signaling
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Year: 2020 PMID： 32130885 PMCID： PMC7088435 DOI： 10.1016/j.cmet.2020.02.003
Source DB: PubMed Journal: Cell Metab ISSN： 1550-4131 Impact factor: 27.287