UGA Research Reveals Nickel Impact on Sterols

In the journal PLoS Genetics, University of Georgia researchers released a significant study. They found that sterol deficit in fungal and mammalian cells is associated with exposure to nickel. This surprising link has significance for our comprehension of sterol biosynthesis and nickel toxicity.

Nickel and Its Participation in Sterol Synthesis

Nickel's Role in Sterols

• Nickel is an important heavy metal that acts as a cofactor for enzymes such as urease in plants, bacteria, and fungi.
• While cholesterol is the major sterol in mammals, ergosterol is similar in fungi.

Research Findings

• Cryptococcus neoformans may live under high nickel content, thereby rejecting the hypothesis that urease contributes a lot.
• Sre1 (sterol response element 1) knock-out mutant had low resistance to nickel, and its gene targets are involved in sterol biosynthesis.
• Nickel promotes the cleander SREBP that is needed to produce enzymes that enable the synthesis of sterol.

The role of ERG25 

• Nickel tolerance was unable in the Sre1 mutant but could be regained by overexpression of the ERG25 gene.

Impact on Human Cells

• Nickel also affected the cholesterol, decreasing it in human cells as in C. neoformans.

Research Questions

• It should be addressed whether other fungi contain ERG25 genes that offer nickel tolerance.
• Determining if the sterol biosynthesis function of ERG25 is necessary for the protein’s nickel tolerance activity.
• Opportunity to offer new therapies 
• Catalase, an antioxidant enzyme, is seen to be involved in nickel tolerance, whereas ERG25 protein, which is required for sterol biosynthesis, seems to enable nickel tolerance.