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Ca(2+)-mediated mitochondrial ROS metabolism augments Wnt/β-catenin pathway activation to facilitate cell differentiation

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Item Type:Article
Title:Ca(2+)-mediated mitochondrial ROS metabolism augments Wnt/β-catenin pathway activation to facilitate cell differentiation
Creators Name:Rharass, T. and Lemcke, H. and Lantow, M. and Kuznetsov, S.A. and Weiss, D.G. and Panáková, D.
Abstract:Emerging evidence suggests that reactive oxygen species (ROS) can stimulate Wnt/{beta}-catenin pathway in a number of cellular processes. However, potential sources of endogenous ROS have not been thoroughly explored. Here, we show that growth factor depletion in human neural progenitor cells induces ROS production in mitochondria. Elevated ROS levels augment activation of Wnt/{beta}-catenin signaling that regulates neural differentiation. We find that growth factor depletion stimulates release of Ca(2+) from the endoplasmic reticulum stores that subsequently accumulates in the mitochondria and triggers ROS production. The inhibition of mitochondrial Ca(2+) uptake with simultaneous growth factor depletion prevents the rise in ROS metabolism. Moreover, low ROS levels block the dissociation of the Wnt effector Dishevelled from Nucleoredoxin. Attenuation of the response amplitudes of pathway effectors delays the onset of Wnt/{beta}-catenin pathway activation and results in markedly impaired neuronal differentiation. Our findings reveal Ca(2+)-mediated ROS metabolic cues that finetune the efficiency of cell differentiation by modulating the extent of the Wnt/{beta}-catenin signaling output.
Keywords:Calcium Signaling, Dishevelled, Mitochondrial Metabolism, Nucleoredoxin, Reactive Oxygen Species (ROS), Redox Signaling, Wnt Pathway, Human Neural Progenitor Cells
Source:Journal of Biological Chemistry
ISSN:0021-9258
Publisher:American Society for Biochemistry and Molecular Biology (U.S.A.)
Volume:289
Number:40
Page Range:27937-27951
Date:3 October 2014
Official Publication:https://doi.org/10.1074/jbc.M114.573519
PubMed:View item in PubMed

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