Ultrasensitive Genetically Encoded Indicator for Hydrogen Peroxide Identifies Roles for the Oxidant in Cell Migration and Mitochondrial Function

Valeriy V Pak, Daria Ezeriņa, Olga G Lyublinskaya, Brandán Pedre, Pyotr A Tyurin-Kuzmin, Natalie M Mishina, Marion Thauvin, David Young, Khadija Wahni, Santiago Agustin Martinez, Alexandra D Demidovich, Yulia G Ermakova, Yulia D Maslova, Arina G Shokhina, Emrah Eroglu, Dmitry S Bilan, Ivan Bogeski, Thomas Michel, Sophie Vriz, Joris MessensVsevolod V Belousov

Research output: Contribution to journalArticle

35 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)642-653.e6
Number of pages12
JournalCell Metabolism
Volume31
Issue number3
DOIs
Publication statusPublished - 3 Mar 2020

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