Phosphomevalonate kinase is a cytosolic protein in humans.
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.
Hogenboom
Sietske
S
Laboratory Genetic Metabolic Diseases, Department of Clinical Chemistry, Emma Children's Hospital, Academic Medical Center, Amsterdam, The Netherlands.
Tuyp
John J M
JJ
Espeel
Marc
M
Koster
Janet
J
Wanders
Ronald J A
RJ
Waterham
Hans R
HR
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
D013729:Terpenes; D017856:Phosphotransferases (Phosphate Group Acceptor); C022371:phosphomevalonate kinase