Peroxisomal protein targeting and identification of peroxisomal targeting signals in cholesterol biosynthetic enzymes

At least three different subcellular compartments, including peroxisomes, a re involved in cholesterol synthesis. Recently, it has been demonstrated th at peroxisomes contain a number of enzymes involved in cholesterol biogenes is that previously were considered to be cytosolic or located in the endopl asmic reticulum. Peroxisomes have been shown to contain acetoacetyl-CoA thi olase, HMG-CoA synthase, HMG-CoA reductase, mevalonate kinase, phosphomeval onate kinase, phosphomevalonate decarboxylase, isopentenyl diphosphate isom erase and FPP synthase. Moreover, the activities of these enzymes are also significantly decreased in liver tissue and fibroblast cells obtained from patients with peroxisomal deficiency diseases. In addition, the cholesterol biosynthetic capacity is severely impaired in cultured skin fibroblasts ob tained ii om patients with peroxisomal deficiency diseases. These findings support the proposal that peroxisomes play an essential role in isoprenoid biosynthesis. This paper presents a review of peroxisomal protein targeting and of recent studies demonstrating the localization of cholesterol biosyn thetic enzymes in peroxisomes and the identification of peroxisomal targeti ng signals in these proteins. (C) 2000 Elsevier Science B.V. All rights res erved.