title: Mevalonate kinase is a cytosolic enzyme in humans.
abstract: In the past decade several reports have appeared which suggest that peroxisomes play a central role in isoprenoid/cholesterol biosynthesis. These suggestions were based primarily on the reported finding of several of the enzymes of the presqualene segment of the biosynthetic pathway in peroxisomes. More recently, however, conflicting results have been reported raising doubt about the postulated role of peroxisomes in isoprenoid biosynthesis, at least in humans. In this study we have studied the subcellular localisation of human mevalonate kinase (MK) using a variety of biochemical and microscopical techniques. These include conventional subcellular fractionation studies, digitonin permeabilisation studies, immunofluorescence microscopy and immunocytochemistry. We exclusively found a cytosolic localisation of both endogenous human MK (human fibroblasts, liver and HEK293 cells) and overexpressed human MK (human fibroblasts, HEK293 cells and CV1 cells). No indication of a peroxisomal localisation was obtained. Our results do not support a central role for peroxisomes in isoprenoid biosynthesis.
authors.affiliation: Laboratory Genetic Metabolic Diseases, Department of Pediatrics, Emma Children's Hospital, Academic Medical Center, Amsterdam.
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; D002463:Cell Membrane Permeability / Q000187:drug effects / Q000502:physiology; D003600:Cytosol / Q000201:enzymology* / Q000378:metabolism; D004072:Digitonin / Q000494:pharmacology; D005347:Fibroblasts / Q000166:cytology / Q000201:enzymology; D006801:Humans; D007668:Kidney / Q000166:cytology / Q000201:enzymology; D008099:Liver / Q000201:enzymology / Q000648:ultrastructure; D008856:Microscopy, Fluorescence; D020675:Peroxisomes / Q000201:enzymology; D017853:Phosphotransferases (Alcohol Group Acceptor) / Q000235:genetics* / Q000378:metabolism*; D013347:Subcellular Fractions / Q000201:enzymology
chemical_list: D017853:Phosphotransferases (Alcohol Group Acceptor); C021796:mevalonate kinase; D004072:Digitonin