Using a yeast model of Parkinson's disease, we found that alpha-synuclein (alpha S) binds to lipid droplets in lipid-loaded, wild-type yeast cells but not to lipid droplets in lipid-loaded, peroxisome-deficient cells (pex3 Delta). Our analysis revealed that pex3 Delta cells have both fewer lipid droplets and smaller lipid droplets than wild-type cells, and that the acyl chains of the phospholipids on the surface of the lipid droplets from pex3 Delta cells are on average shorter (C-16) than those (C-18) on the surface of lipid droplets from wild-type cells. We propose that the shift to shorter (C-18 -> C-16) acyl chains contributes to the reduced binding of alpha S to lipid droplets in pex3 Delta cells. (C) 2013 Elsevier Inc. All rights reserved.