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Mouse Models for Glutathione Peroxidase 4 (GPx4)

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Selenium

Abstract

The selenoperoxidase glutathione peroxidase 4 (GPx4 – also frequently referred to as phospholipid hydroperoxide glutathione peroxidase, PHGPx) is one of the eight glutathione peroxidases in mammals, but the only one known to be essential for early mouse development. GPx4 is emerging as one of the most central selenoproteins, and thus has attracted considerable interest in recent years. Key insights into GPx4 function came from the numerous transgenic and knockout mouse studies performed mainly during the last couple of years, which are summarized here. These investigations not only firmly established a crucial role for GPx4 in male fertility and neuroprotection, but also indicated a major regulatory role of GPx4 in oxidative stress-induced cell death signaling. Beyond this, lipid hydroperoxides (LOOH), downstream of GPx4 inactivation, have been recently shown to control receptor tyrosine kinase (RTK) signaling, thus adding a new layer of complexity to the multifaceted roles of GPx4 in cell signaling and disease development.

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Acknowledgements

This work was supported by the Deutsche Forschungsgemeinschaft (DFG) CO 291/2-3, the DFG Priority Programmes SPP1087 and SPP1190 and a travel fellowship from the European Molecular Biology Laboratory.

Author information

Authors and Affiliations

  1. DZNE – German Center for Neurodegenerative Diseases, 80336, Munich, Germany

    Marcus Conrad

  2. Helmholtz Center Munich, German Research Center for Environmental Health, Institute of Developmental Genetics, Ingolstädter Landstrasse, 85764, Neuherberg, Germany

    Marcus Conrad

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  1. Marcus Conrad
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Correspondence to Marcus Conrad .

Editor information

Editors and Affiliations

  1. National Cancer Institute, Basic Research Laboratory, National Institutes of Health, Bethesda, 20892, Maryland, USA

    Dolph L. Hatfield

  2. University of Hawaii, Monoa, Dole Street 2444, Honolulu, 96822, Hawaii, USA

    Marla J. Berry

  3. , Division of Genetics, Department of Medi, Brigham and Women’s Hospital and Harvard, Avenue Louis Pasteur 77, Boston, 02115, USA

    Vadim N. Gladyshev

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Conrad, M. (2011). Mouse Models for Glutathione Peroxidase 4 (GPx4). In: Hatfield, D., Berry, M., Gladyshev, V. (eds) Selenium. Springer, New York, NY. https://doi.org/10.1007/978-1-4614-1025-6_43

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