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From Selenium Absorption to Selenoprotein Degradation

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Abstract

Selenium is an essential dietary micronutrient. Ingested selenium is absorbed by the intestines and transported to the liver where it is mostly metabolized to selenocysteine (Sec). Sec is then incorporated into selenoproteins, including selenoprotein P (SELENOP), which is secreted into plasma and serves as a source of selenium to other tissues of the body. Herein, we provide an overview of the biology of selenium from its absorption and distribution to selenoprotein uptake and degradation, with a particular focus on the latter. Molecular mechanisms of selenoprotein degradation include the lysosome-mediated pathway for SELENOP and endoplasmic reticulum–mediated degradation of selenoproteins via ubiquitin-activated proteasomal pathways. Ubiquitin-activated pathways targeting full-length selenoproteins include the peroxisome proliferator–activated receptor gamma–dependent pathway and substrate-dependent ubiquitination. An alternate mechanism is utilized for truncated selenoproteins, in which cullin-RING E3 ubiquitin ligase 2 targets the defective proteins for ubiquitin-proteasomal degradation. Selenoproteins, particularly SELENOP, may have their Sec residues reutilized for new selenoprotein synthesis via Sec decomposition. This review will explore these aspects in selenium biology, providing insights to knowledge gaps that remain to be uncovered.

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Acknowledgments

Supported by United States National Institutes of Health grants R01DK47320 (NIDDK), R01DK47320-S1 (Office of Dietary Supplements) and G12MD007601 (NIMHD) to Marla J. Berry, and U54MD007601—subproject 5544 (NIMHD) to Lucia A. Seale.

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  1. Department of Cell and Molecular Biology, John A. Burns School of Medicine, University of Hawaii at Manoa, 651 Ilalo Street, Honolulu, HI, 96813, USA

    Herena Y. Ha, Naghum Alfulaij, Marla J. Berry & Lucia A. Seale

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  1. Herena Y. Ha
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  2. Naghum Alfulaij
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  4. Lucia A. Seale
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Correspondence to Lucia A. Seale.

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Ha, H.Y., Alfulaij, N., Berry, M.J. et al. From Selenium Absorption to Selenoprotein Degradation. Biol Trace Elem Res 192, 26–37 (2019). https://doi.org/10.1007/s12011-019-01771-x

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