Selenium: Tracing Another Essential Element of Ferroptotic Cell Death Original paper
Researched by:
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Divine Aleru
ID
Divine Aleru
Read MoreI am a biochemist with a deep curiosity for the human microbiome and how it shapes human health, and I enjoy making microbiome science more accessible through research and writing. With 2 years experience in microbiome research, I have curated microbiome studies, analyzed microbial signatures, and now focus on interventions as a Microbiome Signatures and Interventions Research Coordinator.
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Metals
Metals
Heavy metals influence microbial pathogenicity in two ways: they can be toxic to microbes by disrupting cellular functions and inducing oxidative stress, and they can be exploited by pathogens to enhance survival, resist treatment, and evade immunity. Understanding metal–microbe interactions supports better antimicrobial and public health strategies.
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Divine Aleru
Read More
Researched by:
-
Divine Aleru
ID
Divine Aleru
Read More
Microbiome Signatures identifies and validates condition-specific microbiome shifts and interventions to accelerate clinical translation. Our multidisciplinary team supports clinicians, researchers, and innovators in turning microbiome science into actionable medicine.
Divine Aleru
What was reviewed?
This review explored the role of selenium in ferroptosis, focusing on its essential involvement through glutathione peroxidase 4 (GPX4), a key selenoenzyme that protects against lipid peroxidation and ferroptosis. It examines the dual role of selenium in regulating iron-dependent lipid peroxidation and the mechanisms through which selenium, via GPX4 and other selenoproteins, helps prevent oxidative damage in various tissues. The review highlights how selenium, beyond its canonical function in GPX4, is involved in a selenium-independent ferroptosis suppressor protein 1 (FSP1)-ubiquinone-NAD(P)H axis, which also suppresses ferroptosis through lipid radical trapping.
Who was reviewed?
The review draws from recent studies and genetic research in animal models, including mouse knockouts of GPX4 and other selenoproteins. These studies investigate the role of selenium in different tissues (e.g., neurons, liver, kidneys) and its interaction with ferroptosis. The paper also discusses selenium’s critical role in neuronal function, specifically in preventing oxidative damage and neurodegeneration, providing insight into selenium deficiency-related diseases such as Alzheimer’s disease, Parkinson’s disease, and epilepsy.
What were the most important findings?
The review identifies selenium as a critical modulator of ferroptosis, especially through the GPX4-GSH pathway, which mitigates oxidative stress by reducing phospholipid hydroperoxides. The review also highlights the selenium-independent system, including the FSP1-CoQ10-NAD(P)H pathway, which operates parallel to GPX4 and lipid peroxidation control. Importantly, the review confirms that deficient selenium levels lead to impaired GPX4 function, increasing susceptibility to ferroptosis, resulting in severe conditions like neurodegeneration and organ failure. The paper also suggests that selenium supplementation can restore GPX4 expression, potentially preventing neurodegenerative diseases. Additionally, the study notes that excess selenium may be toxic, underlining the importance of optimal selenium levels for cellular protection.
What are the greatest implications of this review?
The findings suggest that selenium’s role in ferroptosis could provide a therapeutic target for diseases linked to oxidative damage and ferroptotic cell death, including neurodegenerative diseases and ischemia/reperfusion injury. Selenium supplementation, especially in tissues like the brain and liver, could protect against GPX4 depletion, reducing lipid peroxidation and neurodegeneration. Furthermore, understanding the selenium-independent ferroptosis suppressor protein (FSP1) pathway opens up additional avenues for therapeutic intervention in cancer and degenerative diseases where cell death regulation is key. The paper also emphasizes the potential for pharmacological modulation of selenium-dependent pathways, including GPX4 inhibition in cancer therapies, making selenium a key element in metabolic homeostasis and disease treatment.
Ferroptosis
Ferroptosis links metabolism to disease because it depends on iron handling and membrane lipid chemistry. Tumors, neurodegeneration, and organ injury models often shift ferroptosis sensitivity by changing cystine uptake, glutathione levels, GPX4 activity, and alternative antioxidant pathways such as FSP1–CoQ10.
Glutathione
Glutathione, the body’s most important intracellular antioxidant, plays a far-reaching role in the immune system that goes beyond simply neutralizing oxidative stress. As a crucial player in nutritional immunity, glutathione helps regulate nutrient competition between the host and pathogens, ensuring that pathogens are deprived of essential nutrients, like cysteine, that are critical for their survival. Through its involvement in redox signaling, cytokine production, and immune cell activation, glutathione contributes to immune resilience, particularly under nutrient-limited conditions.