# Selenoprotein-independent biological roles for selenium in selenium deficiency and excess

> **NIH NIH R01** · UNIV OF MASSACHUSETTS MED SCH WORCESTER · 2024 · $343,375

## Abstract

Project Summary
Selenium (Se) is an essential micronutrient with antioxidant function as it is required in the synthesis of 25
different selenoproteins, many of which are antioxidants such as glutathione peroxidases. Observing that
selenium’s antioxidant effects are too rapid and robust to be explained by selenoprotein production alone, we
uncovered a novel biological mechanism for selenium, in which it acts as an electron donor to reduce ubiquinone
to ubiquinol in a reaction that is catalyzed by sulfide quinone oxidoreductase (SQOR). Ubiquinol is a key redox
component in mitochondria, as well as a cellular respiration intermediate, and this mechanism allows selenide
to rapidly suppress lipid peroxidation and trigger cellular respiration. Based on strong preliminary data, we will
examine the hypothesis that this mechanism allows selenium to act as a powerful antioxidant as well as an
alternative electron transport fuel. This mechanism is expected to account for some of the previously known
cytoprotective properties of selenium, explain why selenium deficiency is harmful, as well as introduce novel
selenium-based therapeutic approaches. In Aim 1, we will examine the role of SQOR-catalyzed ubiquinol
formation in the antioxidant role of selenium, as well as its previously unappreciated role as an electron transport
fuel. The beneficial effects of this mechanism on cell-based disease models for cardiomyocyte ischemia, electron
transport dysfunction, and ETC-impairing environmental toxins will be examined. In Aim 2, we will examine the
hypothesis that excess activation of this ubiquinol, membrane-polarizing mechanism is responsible for the
toxicity of high selenium levels. In Aim 3, we will explore the notion that the form of selenium as well as the
delivery route in vivo is key in whether this novel SQOR / ubiquinol mechanism is engaged. The proposal will
result in a mechanistically enhanced understanding of the biological roles of selenium and introduce strategies
to harness selenium biology for therapeutic effects.

## Key facts

- **NIH application ID:** 10894123
- **Project number:** 5R01GM148832-02
- **Recipient organization:** UNIV OF MASSACHUSETTS MED SCH WORCESTER
- **Principal Investigator:** Dohoon Kim
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $343,375
- **Award type:** 5
- **Project period:** 2023-08-01 → 2027-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10894123

## Citation

> US National Institutes of Health, RePORTER application 10894123, Selenoprotein-independent biological roles for selenium in selenium deficiency and excess (5R01GM148832-02). Retrieved via AI Analytics 2026-05-28 from https://api.ai-analytics.org/grant/nih/10894123. Licensed CC0.

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