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

Pak, Valeriy V.; Ezeriņa, Daria; Lyublinskaya, O. G.; Pedre, Brandán; Tyurin‐Kuzmin, Pyotr A.; Mishina, Natalia M.; Thauvin, Marion; Young, Diana; Wahni, Khadija; Gache, Santiago Agustín Martínez; Demidovich, Alexandra D.; Ermakova, Yulia G.; Maslova, Yulia D.; Shokhina, Arina G.; Eroğlu, Emrah; Bilan, Dmitry S.; Bogeski, Ivan; Michel, Thomas; Vriz, Sophie; Messens, Joris; Belousov, Vsevolod V.

doi:10.1016/j.cmet.2020.02.003

Cited by 270 publications

(321 citation statements)

References 64 publications

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“…We next tested whether altering endogenous H 2 O 2 levels would affect Eng2 distribution. Thanks to the use of the improved ratiometric H 2 O 2 sensor HyPer7 22 , we were able to detect, in vivo, the modulation of H 2 O 2 levels after treatment with a pan-NADPH oxidase inhibitor (Nox-i) (Fig. 1f).…”

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H2O2 and Engrailed 2 paracrine activity synergize to shape the zebrafish optic tectum

et al. 2020

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Although a physiological role for redox signaling is now clearly established, the processes sensitive to redox signaling remains to be identified. Ratiometric probes selective for H2O2 have revealed its complex spatiotemporal dynamics during neural development and adult regeneration and perturbations of H2O2 levels disturb cell plasticity and morphogenesis. Here we ask whether endogenous H2O2 could participate in the patterning of the embryo. We find that perturbations of endogenous H2O2 levels impact on the distribution of the Engrailed homeoprotein, a strong determinant of midbrain patterning. Engrailed 2 is secreted from cells with high H2O2 levels and taken up by cells with low H2O2 levels where it leads to increased H2O2 production, steering the directional spread of the Engrailed gradient. These results illustrate the interplay between protein signaling pathways and metabolic processes during morphogenetic events.

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H2O2 and Engrailed 2 paracrine activity synergize to shape the zebrafish optic tectum

et al. 2020

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“…It could also be coupled to redox signaling (discussed below) [ 230 ]. Conversely, defective antioxidant defense will favor mitochondrial H 2 O 2 release [ 231 ] or reactivity with transition metal ions to produce ● OH (reaction 14) [ 232 ]. Knowledge of oocyte/early zygote antioxidant defense is limited, so their capacity to rebuff an ART-induced increase in H 2 O 2 is unclear.…”

Section: A Framework For Interpreting the Role Of Mitochondrial Romentioning

confidence: 99%

Mechanisms of Mitochondrial ROS Production in Assisted Reproduction: The Known, the Unknown, and the Intriguing

Cobley

2020

Antioxidants

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The consensus that assisted reproduction technologies (ART), like in vitro fertilization, to induce oxidative stress (i.e., the known) belies how oocyte/zygote mitochondria—a major presumptive oxidative stressor—produce reactive oxygen species (ROS) with ART being unknown. Unravelling how oocyte/zygote mitochondria produce ROS is important for disambiguating the molecular basis of ART-induced oxidative stress and, therefore, to rationally target it (e.g., using site-specific mitochondria-targeted antioxidants). I review the known mechanisms of ROS production in somatic mitochondria to critique how oocyte/zygote mitochondria may produce ROS (i.e., the unknown). Several plausible site- and mode-defined mitochondrial ROS production mechanisms in ART are proposed. For example, complex I catalyzed reverse electron transfer-mediated ROS production is conceivable when oocytes are initially extracted due to at least a 10% increase in molecular dioxygen exposure (i.e., the intriguing). To address the term oxidative stress being used without recourse to the underlying chemistry, I use the species-specific spectrum of biologically feasible reactions to define plausible oxidative stress mechanisms in ART. Intriguingly, mitochondrial ROS-derived redox signals could regulate embryonic development (i.e., their production could be beneficial). Their potential beneficial role raises the clinical challenge of attenuating oxidative damage while simultaneously preserving redox signaling. This discourse sets the stage to unravel how mitochondria produce ROS in ART, and their biological roles from oxidative damage to redox signaling.

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“…The analytical challenges of measuring reactive species directly are, therefore, considerable [211][212][213][214]. While significant analytical challenges have been surmounted (e.g., real time ratio-metric H 2 O 2 and GSH measurement [215][216][217][218][219]), it is essential to measure what reactive species are doing by chemically foot-printing their biological reactivity. For many years, the scope of chemical foot-printing was narrowed by oxidative stress being viewed as solely deleterious and a resultant focus on measuring oxidative macromolecule adducts.…”

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Immunological Techniques to Assess Protein Thiol Redox State: Opportunities, Challenges and Solutions

Cobley

Husi

2020

Antioxidants

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To understand oxidative stress, antioxidant defense, and redox signaling in health and disease it is essential to assess protein thiol redox state. Protein thiol redox state is seldom assessed immunologically because of the inability to distinguish reduced and reversibly oxidized thiols by Western blotting. An underappreciated opportunity exists to use Click PEGylation to realize the transformative power of simple, time and cost-efficient immunological techniques. Click PEGylation harnesses selective, bio-orthogonal Click chemistry to separate reduced and reversibly oxidized thiols by selectively ligating a low molecular weight polyethylene glycol moiety to the redox state of interest. The resultant ability to disambiguate reduced and reversibly oxidized species by Western blotting enables Click PEGylation to assess protein thiol redox state. In the present review, to enable investigators to effectively harness immunological techniques to assess protein thiol redox state we critique the chemistry, promise and challenges of Click PEGylation.

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

Cited by 270 publications

References 64 publications

H2O2 and Engrailed 2 paracrine activity synergize to shape the zebrafish optic tectum

H2O2 and Engrailed 2 paracrine activity synergize to shape the zebrafish optic tectum

Mechanisms of Mitochondrial ROS Production in Assisted Reproduction: The Known, the Unknown, and the Intriguing

Immunological Techniques to Assess Protein Thiol Redox State: Opportunities, Challenges and Solutions

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