title: Phosphomevalonate kinase is a cytosolic protein in humans.
abstract: In the past decade, a predominant peroxisomal localization has been reported for several enzymes functioning in the presqualene segment of the cholesterol/isoprenoid biosynthesis pathway. More recently, however, conflicting results have been reported raising doubts about the postulated role of peroxisomes in isoprenoid biosynthesis, at least in humans. In this study, we have determined the subcellular localization of human phosphomevalonate kinase using a variety of biochemical and microscopic techniques, including conventional subcellular fractionation studies, digitonin permeabilization studies, immunofluorescence, and immunoelectron microscopy. We found an exclusive cytosolic localization of both endogenously expressed human phosphomevalonate kinase (in human fibroblasts, human liver, and HEK293 cells) and overexpressed human phosphomevalonate kinase (in human fibroblasts, HEK293 cells, and CV1 cells). No indication of a peroxisomal localization was obtained. Our results do not support a central role of peroxisomes in isoprenoid biosynthesis.
authors.affiliation: Laboratory Genetic Metabolic Diseases, Department of Clinical Chemistry, Emma Children's Hospital, Academic Medical Center, Amsterdam, The Netherlands.
authors.forename: Sietske
authors.initials: S
authors.lastname: Hogenboom
authors.forename: John J M
authors.initials: JJ
authors.lastname: Tuyp
authors.forename: Marc
authors.initials: M
authors.lastname: Espeel
authors.forename: Janet
authors.initials: J
authors.lastname: Koster
authors.forename: Ronald J A
authors.initials: RJ
authors.lastname: Wanders
authors.forename: Hans R
authors.initials: HR
authors.lastname: Waterham
mesh_terms: D002460:Cell Line; D002478:Cells, Cultured; D003600:Cytosol / Q000201:enzymology*; D005347:Fibroblasts / Q000166:cytology; D006801:Humans; D007668:Kidney / Q000166:cytology; D008099:Liver / Q000166:cytology; D008854:Microscopy, Electron; D020675:Peroxisomes / Q000201:enzymology; D017856:Phosphotransferases (Phosphate Group Acceptor) / Q000032:analysis*; D013729:Terpenes
chemical_list: D013729:Terpenes; D017856:Phosphotransferases (Phosphate Group Acceptor); C022371:phosphomevalonate kinase