Squalene and Coenzyme Q are crucial in suppressing cholesterol mediated ferroptosis

Feb 19^th, 2024 – New York, USA. Ferroptosis is a form of programmed cell death triggered by the accumulation of iron-dependent lipid peroxides on cell membranes. The regulation of ferroptosis is associated with multiple signalling pathways, and mounting evidence indicates its involvement in regulating systemic disorders, including neurodegenerative diseases and organ damage¹.

A team of researchers at Shandong University in China, conducted a genetic and pharmacological study to assess the role of cholesterol metabolism in safeguarding cells against ferroptosis. The results indicate that ferroptosis can be induced through either the extrinsic or intrinsic pathways. The study demonstrated that altering cholesterol levels can affect the susceptibility of cells to ferroptosis. These noteworthy findings were published in the prestigious journal ‘Nature’².

Fatty acid metabolism, an integral component of lipid metabolism, plays a significant role in ferroptosis, with the mevalonate pathway being responsible for endogenous cholesterol biosynthesis. Cholesterol and certain sterol metabolites in the mevalonate pathway serve as regulators of cholesterol metabolism.

In this particular study, researchers hypothesized that cholesterol and its metabolites could influence cell sensitivity to ferroptosis. A small-scale screening of commercially available sterol metabolites/derivatives as possible modulators of ferroptosis led the researcher to identify cholesterol and desmosterol as endogenous ferroptosis inhibitors. Their findings revealed that these two metabolites in the mevalonate pathway exerted their anti-ferroptotic functions through the same mechanism: accelerating the degradation of Squalene Epoxidase (SQLE) to elevate intracellular levels of both Squalene and Coenzyme Q (CoQ).

Coenzyme Q and Squalene, two important lipid metabolites, have been identified as novel lipid peroxide scavengers, alongside the GPX4 protein. The findings suggest that boosting cellular concentrations of Squalene and CoQ can impede ferroptosis, emphasizing the vital roles of both Squalene and CoQ as significant downstream factors for cholesterol and desmosterol in the regulation of ferroptosis.

“Understanding the intricate interplay between lipid metabolism and ferroptosis opens new avenues for nutritional strategies. The study’s discovery suggests the pivotal role of cholesterol and its metabolites in cellular health, offering insights into potential dietary interventions, such as Squalene and CoQ, for preventing ferroptosis-related disorders”, said Dr. Ariati Aris, Scientific Affairs Specialist at PhytoGaia.

 “This discovery adds to our scientific knowledge, highlighting the numerous health benefits linked to potent lipid peroxide scavengers like Squalene and CoQ10. If the antioxidant system is disrupted, it can lead to the excessive activation of ferroptosis. This open up exciting opportunities for innovative dietary supplements or a well-balanced diet enriched with plant Squalene and CoQ10, aimed at maintaining cellular integrity and promoting overall well-being. PhytoGaia supplies a natural plant-based squalene called STGaia^TM as a sustainable and economical alternative to animal-based squalene”, added Mr. Bryan See, Vice President of PhytoGaia.

References

1. Hu, W. et al. 2022. Ferroptosis and Its Role in Chronic Diseases. Cells, 11, 2040.
2.  Sun, Q. et al. Cholesterol mediated ferroptosis suppression reveals essential roles of Coenzyme Q and squalene.Commun Biol 6, Nat. 1108.