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Journal of Lipid Research, Vol. 45, 697-705, April 2004
Copyright © 2004 by American Society for Biochemistry and Molecular Biology

Phosphomevalonate kinase is a cytosolic protein in humans

Sietske Hogenboom^*, John J. M. Tuyp^*, Marc Espeel, Janet Koster^*, Ronald J. A. Wanders^* and Hans R. Waterham^1,*

^* Laboratory Genetic Metabolic Diseases, Departments of Clinical Chemistry and Pediatrics, Emma Children's Hospital, Academic Medical Center, Amsterdam, The Netherlands
Department of Anatomy, Embryology, Histology, and Medical Physics, University of Gent, Gent, Belgium

¹ To whom correspondence should be addressed. e-mail: h.r.waterham{at}amc.uva.nl

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.

Abbreviations: CAT, catalase; FHC, familial hypercholesterolemia; GFP, green fluorescent protein; MMP7, metallo-matrix protein 7; PGI, phosphoglucoisomerase; PMK, phosphomevalonate kinase; PTS, peroxisomal targeting sequence; ZS, Zellweger syndrome

Supplementary key words cholesterol biosynthesis • isoprenoid • peroxisomes • Zellweger syndrome

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