Mutations in yeast ARV1 alter intracellular sterol distribution and are complemented by human ARV1

Intracellular cholesterol redistribution between membranes and its subseque nt esterification are critical aspects of lipid homeostasis that prevent fr ee sterol toxicity. To identify genes that mediate sterol trafficking, we s creened for yeast mutants that were inviable in the absence of sterol ester ification. Mutations in the novel gene, ARV1, render cells dependent on ste rol esterification for growth, nystatin-sensitive, temperature-sensitive, a nd anaerobically inviable. Cells lacking Arv1p display altered intracellula r sterol distribution and are defective in sterol uptake, consistent with a role for Arv1p in trafficking sterol into the plasma membrane. Human ARV1, a predicted sequence ortholog of yeast ARV1, complements the defects assoc iated with deletion of the yeast gene. The genes are predicted to encode tr ansmembrane proteins with potential zinc-binding motifs. We propose that AR V1 is a novel mediator of eukaryotic sterol homeostasis.