Unexpected Correlation Between Cholesterol and Nickel Toxicity

• Fungi lacking the Sre1 protein are sensitive to nickel, a conserved gene in all animals.
• Nickel is needed for the normal function of an enzyme called urease in plants, bacteria, and fungi.
• Tolerance to nickel increases when fungal cells overexpress a gene called ERG25, which encodes an enzyme.
• Nickel toxicity was previously unknown to be related to sterol biosynthesis in fungi and animals.
• Nickel is a contact allergen and carcinogenic in a significant fraction of people.
• Sterols, a chemical component of cell membranes, are crucial in plants, animals, and fungi.
• Drugs like statins are used to reduce cholesterol biosynthesis to avoid adverse outcomes.
• Researchers from the University of Georgia discovered that a wild-type Cryptococcus neoformans strain could grow in a medium supplemented with up to 250 millimoles of nickel sulphate.
• Nickel triggered the cleavage of SREBP, causing C.neoformans to become hypersensitive to nickel.
• Overexpression of the ERG25 gene alone restored nickel tolerance to the strain.
• The research team is addressing questions about the conferring of nickel tolerance in a Cryptococcus strain lacking its own ERG25 gene, the sterol biosynthetic function of the ERG25 enzyme, and the role of the human gene corresponding to ERG25 in nickel tolerance in human cells.