Farnesyl-diphosphate synthase is localized in peroxisomes.

In this study, we have investigated the subcellular localization of farnesyl-diphosphate synthase (FPP synthase). FPP synthase produces FPP, which is utilized in the synthesis of squalene, cholesterol, farnesylated and geranylgeranylated proteins, dolichols, coenzyme Q, and the isoprenoid moiety of heme a. This enzyme is found in the 100,000 x g supernatant fraction of cells or tissues and has been considered to be a cytoplasmic protein. In this study, analysis of FPP synthase activity and protein in fractionated rat liver together with immunofluorescent and immunoelectron microscopy studies demonstrated unequivocally that FPP synthase is largely localized in peroxisomes. These data, in combination with the previous observation that mevalonate kinase is predominantly localized in peroxisomes, suggest that peroxisomes are the major site of synthesis of FPP from mevalonate. We also demonstrate that in liver tissue obtained from patients with peroxisomal deficiency diseases (Zellweger syndrome and neonatal adrenoleukodystrophy), the activities of five enzymes involved in isoprenoid synthesis, namely mevalonate kinase, phosphomevalonate kinase, mevalonate-diphosphate decarboxylase, isopentenyl-diphosphate isomerase, and FPP synthase, are significantly reduced, consistent with a peroxisomal localization of these enzymes.

• Publication year

  1994

• Venue

  Journal of Biological Chemistry

• Publication date

  1994-05-13

• Fields of study

  Biology, Medicine, Chemistry

• Identifiers
  DOI 10.1016/s0021-9258(17)36769-8PMID 8188698
• External record

  Open on Semantic Scholar

• Source metadata

  Semantic Scholar, PubMed

• No claims are published for this paper.

• No concepts are published for this paper.

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