The DOI matches its Crossref record; 4 of the 4 references it cites were found in a registry or an index.
Mitochondrial glutathione peroxidase 4 disruption causes male infertility
Open accessAbstract
Selenium is linked to male fertility. Glutathione peroxidase 4 (GPx4), first described as an antioxidant enzyme, is the predominant selenoenzyme in testis and has been suspected of being vital for spermatogenesis. Cytosolic, mitochondrial, and nuclear isoforms are all encoded by the same gene. While disruption of entire GPx4 causes early embryonic lethality in mice, inactivation of nuclear GPx4 does not impair embryonic development or fertility. Here, we show that deletion of mitochondrial GPx4 (mGPx4) allows both normal embryogenesis and postnatal development, but causes male infertility. Infertility was associated with impaired sperm quality and severe structural abnormalities in the midpiece of spermatozoa. Knockout sperm display higher protein thiol content and recapitulate features typical of severe selenodeficiency. Interestingly, male infertility induced by mGPx4 depletion could be bypassed by intracytoplasmic sperm injection. We also show for the first time that mGPx4 is the prevailing GPx4 product in male germ cells and that mGPx4 disruption has no effect on proliferation or apoptosis of germinal or somatic tissue. Our study finally establishes that mitochondrial GPx4 confers the vital role of selenium in mammalian male fertility and identifies cytosolic GPx4 as the only GPx4 isoform being essential for embryonic development and apoptosis regulation.—Schneider, M., Forster, H., Boersma, A., Seiler, A., Wehnes, H., Sinowatz, F., Neumüller, C., Deutsch, M. J., Walch, A., Hrabede Angelis, M., Wurst, W., Ursini, F., Roveri, A., Maleszewski, M., Maiorino, M. Conrad, M. Mitochondrial glutathione peroxidase 4 disruption causes male infertility. FASEB J . 23, 3233–3242 (2009). www.fasebj.org
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Seiler, A., Schneider, M., Förster, H., Roth, S., Wirth, E. K., Culmsee, C., Plesnila, N., Kremmer, E., Rådmark, O., Wurst, W., et al. (2008) · Cell Metabolism · doi:10.1016/j.cmet.2008.07.005 · Cited by 1,470
Self-citationUrsini, F., Maiorino, M., Valente, M., Ferri, L., & Gregolin, C. (1982) · Biochimica et Biophysica Acta (BBA) - Lipids and Lipid Metabolism · doi:10.1016/0005-2760(82)90150-3 · Cited by 884
Yant, L. J., Ran, Q., Rao, L., Van Remmen, H., Shibatani, T., Belter, J. G., Motta, L., Richardson, A., & Prolla, T. A. (2003) · Free Radical Biology and Medicine · doi:10.1016/s0891-5849(02)01360-6 · Cited by 797 · cited 2×
“The complexity of gene expression in different tissues and early embryonic lethality of GPx4-knockout (KO) mice have precluded so far dissection of the individual functions of each GPx4 product (18).”
BackgroundConrad, M., Jakupoglu, C., Moreno, S. G., Lippl, S., Banjac, A., Schneider, M., Beck, H., Hatzopoulos, A. K., Just, U., Sinowatz, F., et al. (2004) · Molecular and Cellular Biology · doi:10.1128/mcb.24.21.9414-9423.2004 · Cited by 485
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Cited by
Inactivation of the ferroptosis regulator Gpx4 triggers acute renal failure in mice
Friedmann Angeli, J. P., Schneider, M., Proneth, B., Tyurina, Y. Y., Tyurin, V. A., Hammond, V. J., Herbach, N., Aichler, M., Walch, A., Eggenhofer, E., et al. (2014) · Nature Cell Biology · doi:10.1038/ncb3064 · Cited by 3,732
Self-citationTargeting Ferroptosis as a Vulnerability in Cancer
Lei, G., Zhuang, L., & Gan, B. (2022) · Nature reviews. Cancer · doi:10.1038/s41568-022-00459-0 · Cited by 2,252
Lipid peroxidation and ferroptosis: The role of GSH and GPx4
Ursini, F., & Maiorino, M. (2020) · Free Radical Biology and Medicine · doi:10.1016/j.freeradbiomed.2020.02.027 · Cited by 1,954
Self-citationBrigelius-Flohé, R., & Maiorino, M. (2013) · Biochimica et Biophysica Acta (BBA) - General Subjects · doi:10.1016/j.bbagen.2012.11.020 · Cited by 1,904
Self-citationThe multifaceted contributions of mitochondria to cellular metabolism
Spinelli, J. B., & Haigis, M. C. (2018) · Nature Cell Biology · doi:10.1038/s41556-018-0124-1 · Cited by 1,935
Metadata
- Authors
- Schneider, M., Forster, H., Boersma, A., Seiler, A., Wehnes, H., Sinowatz, F., Neumüller, C., Deutsch, M. J., Walch, A., de Angelis, M. H., Wurst, W., Ursini, F., Roveri, A., Maleszewski, M., Maiorino, M., & Conrad, M.
- Venue
- The FASEB Journal
- Publisher
- Wiley
- Published
- 2009-05-05
- Volume
- 23
- Issue
- 9
- Pages
- 3233-3242
- ISSN
- 0892-6638 (ISSN-L)
- 1530-6860
- OpenAlex
- W2105171996
- Cited by
- 332
- References
- 4
- FWCI
- 22.23
- Type
- journal article
- Language
- en
- Open access
- green
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- Schneider, M., Forster, H., Boersma, A., Seiler, A., Wehnes, H., Sinowatz, F., Neumüller, C., Deutsch, M. J., Walch, A., de Angelis, M. H., Wurst, W., Ursini, F., Roveri, A., Maleszewski, M., Maiorino, M., & Conrad, M. (2009). Mitochondrial glutathione peroxidase 4 disruption causes male infertility. The FASEB Journal. https://doi.org/10.1096/fj.09-132795
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