Red fluorescent genetically encoded indicator for intracellular hydrogen peroxide

Yulia G. Ermakova; Dmitry S. Bilan; Mikhail E. Matlashov; Natalia M. Mishina; Ksenia N. Markvicheva; Oksana M. Subach; Fedor V. Subach; Ivan Bogeski; Markus Hoth; Grigori Enikolopov; Vsevolod V. Belousov

doi:10.1038/ncomms6222

Red fluorescent genetically encoded indicator for intracellular hydrogen peroxide

Yulia G. Ermakova, Dmitry S. Bilan, Mikhail E. Matlashov, Natalia M. Mishina, Ksenia N. Markvicheva, Oksana M. Subach, Fedor V. Subach, Ivan Bogeski, Markus Hoth, Grigori Enikolopov, Vsevolod V. Belousov

Research output: Contribution to journal › Article › peer-review

168 Scopus citations

Abstract

Reactive oxygen species (ROS) are conserved regulators of numerous cellular functions, and overproduction of ROS is a hallmark of various pathological processes. Genetically encoded fluorescent probes are unique tools to study ROS production in living systems of different scale and complexity. However, the currently available recombinant redox sensors have green emission, which overlaps with the spectra of many other probes. Expanding the spectral range of recombinant in vivo ROS probes would enable multiparametric in vivo ROS detection. Here we present the first genetically encoded red fluorescent sensor for hydrogen peroxide detection, HyPerRed. The performance of this sensor is similar to its green analogues. We demonstrate the utility of the sensor by tracing low concentrations of H₂O₂ produced in the cytoplasm of cultured cells upon growth factor stimulation. Moreover, using HyPerRed we detect local and transient H₂O₂ production in the mitochondrial matrix upon inhibition of the endoplasmic reticulum Ca²⁺ uptake.

Original language	English (US)
Article number	5222
Journal	Nature communications
Volume	5
DOIs	https://doi.org/10.1038/ncomms6222
State	Published - 2014
Externally published	Yes

ASJC Scopus subject areas

Chemistry(all)
Biochemistry, Genetics and Molecular Biology(all)
Physics and Astronomy(all)

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10.1038/ncomms6222

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@article{dbe2b03bd4d04ff791cf082f37fbbaff,

title = "Red fluorescent genetically encoded indicator for intracellular hydrogen peroxide",

abstract = "Reactive oxygen species (ROS) are conserved regulators of numerous cellular functions, and overproduction of ROS is a hallmark of various pathological processes. Genetically encoded fluorescent probes are unique tools to study ROS production in living systems of different scale and complexity. However, the currently available recombinant redox sensors have green emission, which overlaps with the spectra of many other probes. Expanding the spectral range of recombinant in vivo ROS probes would enable multiparametric in vivo ROS detection. Here we present the first genetically encoded red fluorescent sensor for hydrogen peroxide detection, HyPerRed. The performance of this sensor is similar to its green analogues. We demonstrate the utility of the sensor by tracing low concentrations of H2O2 produced in the cytoplasm of cultured cells upon growth factor stimulation. Moreover, using HyPerRed we detect local and transient H2O2 production in the mitochondrial matrix upon inhibition of the endoplasmic reticulum Ca2+ uptake.",

author = "Ermakova, {Yulia G.} and Bilan, {Dmitry S.} and Matlashov, {Mikhail E.} and Mishina, {Natalia M.} and Markvicheva, {Ksenia N.} and Subach, {Oksana M.} and Subach, {Fedor V.} and Ivan Bogeski and Markus Hoth and Grigori Enikolopov and Belousov, {Vsevolod V.}",

note = "Funding Information: We thank Tobias Dick (DKFZ) for roGFP2-Grx1 expression vectors, Michael Davidson (FSU) for the EGFP-IMS vector and Nicolas Demaurex for the SypHer-mito vector. This work was supported by SFB1027 project C4 (to I.B.), the DFG grant BO3643/3-1 (to I.B.), SFB 894 project A1 (to M.H.), the Russian foundation for basic research (13-04-40333-H to V.V.B), Molecular and Cell Biology program of Russian Academy of Sciences (V.V.B), National Institute of Aging (grant R01AG040209 to G.E.) and Russian Ministry of Education and Science (grant 11.G34.31.0071 to G.E.). Russian Science Foundation supported mitochondrial imaging experiments (14-14-00747 to V.V.B.). Publisher Copyright: {\textcopyright} 2014 Macmillan Publishers Limited. All rights reserved.",

year = "2014",

doi = "10.1038/ncomms6222",

language = "English (US)",

volume = "5",

journal = "Nature Communications",

issn = "2041-1723",

publisher = "Nature Publishing Group",

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TY - JOUR

T1 - Red fluorescent genetically encoded indicator for intracellular hydrogen peroxide

AU - Ermakova, Yulia G.

AU - Bilan, Dmitry S.

AU - Matlashov, Mikhail E.

AU - Mishina, Natalia M.

AU - Markvicheva, Ksenia N.

AU - Subach, Oksana M.

AU - Subach, Fedor V.

AU - Bogeski, Ivan

AU - Hoth, Markus

AU - Enikolopov, Grigori

AU - Belousov, Vsevolod V.

N1 - Funding Information: We thank Tobias Dick (DKFZ) for roGFP2-Grx1 expression vectors, Michael Davidson (FSU) for the EGFP-IMS vector and Nicolas Demaurex for the SypHer-mito vector. This work was supported by SFB1027 project C4 (to I.B.), the DFG grant BO3643/3-1 (to I.B.), SFB 894 project A1 (to M.H.), the Russian foundation for basic research (13-04-40333-H to V.V.B), Molecular and Cell Biology program of Russian Academy of Sciences (V.V.B), National Institute of Aging (grant R01AG040209 to G.E.) and Russian Ministry of Education and Science (grant 11.G34.31.0071 to G.E.). Russian Science Foundation supported mitochondrial imaging experiments (14-14-00747 to V.V.B.). Publisher Copyright: © 2014 Macmillan Publishers Limited. All rights reserved.

PY - 2014

Y1 - 2014

N2 - Reactive oxygen species (ROS) are conserved regulators of numerous cellular functions, and overproduction of ROS is a hallmark of various pathological processes. Genetically encoded fluorescent probes are unique tools to study ROS production in living systems of different scale and complexity. However, the currently available recombinant redox sensors have green emission, which overlaps with the spectra of many other probes. Expanding the spectral range of recombinant in vivo ROS probes would enable multiparametric in vivo ROS detection. Here we present the first genetically encoded red fluorescent sensor for hydrogen peroxide detection, HyPerRed. The performance of this sensor is similar to its green analogues. We demonstrate the utility of the sensor by tracing low concentrations of H2O2 produced in the cytoplasm of cultured cells upon growth factor stimulation. Moreover, using HyPerRed we detect local and transient H2O2 production in the mitochondrial matrix upon inhibition of the endoplasmic reticulum Ca2+ uptake.

AB - Reactive oxygen species (ROS) are conserved regulators of numerous cellular functions, and overproduction of ROS is a hallmark of various pathological processes. Genetically encoded fluorescent probes are unique tools to study ROS production in living systems of different scale and complexity. However, the currently available recombinant redox sensors have green emission, which overlaps with the spectra of many other probes. Expanding the spectral range of recombinant in vivo ROS probes would enable multiparametric in vivo ROS detection. Here we present the first genetically encoded red fluorescent sensor for hydrogen peroxide detection, HyPerRed. The performance of this sensor is similar to its green analogues. We demonstrate the utility of the sensor by tracing low concentrations of H2O2 produced in the cytoplasm of cultured cells upon growth factor stimulation. Moreover, using HyPerRed we detect local and transient H2O2 production in the mitochondrial matrix upon inhibition of the endoplasmic reticulum Ca2+ uptake.

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SN - 2041-1723

VL - 5

JO - Nature Communications

JF - Nature Communications

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ER -

Red fluorescent genetically encoded indicator for intracellular hydrogen peroxide

Abstract

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