Selenium reduction of ubiquinone via SQOR suppresses ferroptosis

Lee, N.; Park, S. J.; Lange, M.; Tseyang, T.; Doshi, M. B.; Kim, T.; Song, Y.; Kim, D.; Greer, P. L.; Olzmann, J. A.; Spinelli, J.

doi:10.1101/2023.04.13.535674

bioRxiv · 10.1101/2023.04.13.535674

Selenium reduction of ubiquinone via SQOR suppresses ferroptosis

Lee, N.·Park, S. J.·Lange, M.·Tseyang, T.·Doshi, M. B.·Kim, T.·Song, Y.·Kim, D.·Greer, P. L.·Olzmann, J. A.·Spinelli, J.

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Abstract

The canonical biological function of selenium is in the production of selenocysteine residues of selenoproteins, and this forms the basis for its role as an essential antioxidant and cytoprotective micronutrient. Here, we demonstrate that selenium, via its metabolic intermediate hydrogen selenide, efficiently donates its electrons to ubiquinone to form ubiquinol in the mitochondria through catalysis by sulfide quinone oxidoreductase (SQOR). Hydrogen selenide is superior to hydrogen sulfide as an electron donor owing to its larger valence shell. We show that this mechanism, independently of selenoprotein production, protects against ferroptosis via ubiquinol production in a manner that depends on xCT mediated selenide formation and SQOR activity. Our findings identify a regulatory mechanism against ferroptosis that implicates SQOR and expands our understanding of selenium in biology.

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Lee, N., Park, S. J., Lange, M., Tseyang, T., Doshi, M. B., Kim, T., Song, Y., Kim, D., Greer, P. L., Olzmann, J. A., Spinelli, J.. 2023-04-13. Selenium reduction of ubiquinone via SQOR suppresses ferroptosis. https://doi.org/10.1101/2023.04.13.535674

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