Mevalonate kinase is predominantly localized in peroxisomes and is defective in patients with peroxisome deficiency disorders.

Identification of peroxisomal targeting signals in cholesterol biosynthetic enzymes: AA-CoA thiolase, HMG-CoA synthase, MPPD, and FPP synthase

“…We conclude from these data that the targeting of MvK fusion proteins to peroxisomes is either irreversibly obstructed because of interference from the reporter or epitope tag, or that the targeting signal is no longer accessible to the receptor, or that the protein has significantly changed conformation because of the additional sequences making it unrecognizable to the receptor. It is clear, however, that full-length expression constructs of MvK, without epitope tags, are targeted to peroxisomes, as previously shown (19). Table 3 summarizes the peroxisomal targeting signals identified to date in the cholesterol biosynthetic enzymes.…”

“…The peroxisomal localization of MvK, which phosphorylates mevalonate in the fourth reaction of the cholesterol biosynthetic pathway, has been conclusively demonstrated (18,19). On analysis of the amino acid sequence for MvK a putative PTS-2 has been identified that fits the consensus sequence (KVX 5 HA).…”

“…The third reaction of the pathway catalyzed by HMG-CoA reductase, the rate-limiting step in cholesterol biosynthesis, has been localized to both the endoplasmic reticulum (ER) and peroxisomes (15 -17). Both mevalonate kinase (MvK) (18,19) and farnesyl diphos-phate (FPP) synthase (20,21) have been shown by immunofluorescence and immunoelectron microscopy to be predominantly peroxisomal. Furthermore, the enzymes catalyzing reactions between MvK and FPP synthase, phosphomevalonate kinase (PMvK), mevalonate diphosphate decarboxylase (MPPD), and isopentenyl diphosphate (IPP) isomerase, have been suggested to be peroxisomal on the basis of studies utilizing permeabilized cells in which the cytosol has been removed (22).…”

“…While the studies demonstrating activities of AA-CoA thiolase, HMG-CoA synthase, PMvK, MPPD, and IPP isomerase (11)(12)(13)(14)22) and the immunofluorescence and immunoelectron microscopy studies with MvK and FPP synthase (19,20,23) were suggestive of a peroxisomal localization of these enzymes, the specific peroxisomal targeting signals had yet to be identified. However, we have shown that PMvK contains a consensus PTS-1 (SRL), which is required for its localization to peroxisomes (26).…”

Characterization of phosphomevalonate kinase: chromosomal localization, regulation, and subcellular targeting

“…In contrast to their previously believed cytosolic location, several enzymes in the cholesterol biosynthetic pathway have recently been discovered to reside in peroxisomes. Specifically, enzymatic activities for acetoacetyl CoA thiolase (6), HMG-CoA synthase (7), HMG-CoA reductase (8,9), mevalonate kinase (MvK) (10), and farnesyl diphosphate synthase (FPPS) (11) have been localized to peroxisomes. Both MvK and FPP synthase have been shown by immunofluorescence and immunoelectron microscopy to be predominantly peroxisomal (10,11).…”