Influence of peroxisome proliferator-activated receptor α on ubiquinone biosynthesis

Mikael Turunen, Jeffrey Maurice Peters, Frank J. Gonzalez, Sophia Schedin, Gustav Dallner

Research output: Contribution to journalArticle

33 Citations (Scopus)

Abstract

The control of ubiquinone biosynthesis by peroxisome proliferators was investigated using peroxisome proliferator activated receptor α (PPARα)-null mice. Administration of 2-(diethylhexyl)phthalate to control mice resulted in elevated ubiquinone levels in the liver, while dolichol, dolichyl-P and cholesterol concentrations remained unchanged. In PPARα-null mice, the level of these lipids were similar to control levels and administration of the peroxisome proliferator did not increase the levels of ubiquinone. The increase in ubiquinone levels was the result of increased synthesis. Induction was most pronounced in liver, kidney and heart, which have relatively high levels of PPARα. When the tissue concentration of hydrogen peroxide was elevated by inhibition of catalase activity with aminotriazole, the amount of ubiquinone was not increased, suggesting that the induction of ubiquinone synthesis occured through a direct mechanism. The activities of branch-point enzymes FPP-synthase, squalene synthase, cis-prenyltransferase, trans-prenyltransferase and NPHB-transferase were substantially increased in control but not in PPARα-null mice after treatment with peroxisome proliferators. These data suggest that the induction of ubiquinone biosynthesis after administration of peroxisome proliferators is dependent on the PPARα through regulation of some of the mevalonate pathway enzymes. (C) 2000 Academic Press.

Original languageEnglish (US)
Pages (from-to)607-614
Number of pages8
JournalJournal of Molecular Biology
Volume297
Issue number3
DOIs
StatePublished - Mar 31 2000

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Peroxisome Proliferator-Activated Receptors
Ubiquinone
Peroxisome Proliferators
Farnesyl-Diphosphate Farnesyltransferase
Dimethylallyltranstransferase
Diethylhexyl Phthalate
Dolichol
Amitrole
Mevalonic Acid
Liver
Enzymes
Transferases
Catalase
Hydrogen Peroxide
Cholesterol
Kidney
Lipids

All Science Journal Classification (ASJC) codes

  • Structural Biology
  • Molecular Biology

Cite this

Turunen, Mikael ; Peters, Jeffrey Maurice ; Gonzalez, Frank J. ; Schedin, Sophia ; Dallner, Gustav. / Influence of peroxisome proliferator-activated receptor α on ubiquinone biosynthesis. In: Journal of Molecular Biology. 2000 ; Vol. 297, No. 3. pp. 607-614.
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Influence of peroxisome proliferator-activated receptor α on ubiquinone biosynthesis. / Turunen, Mikael; Peters, Jeffrey Maurice; Gonzalez, Frank J.; Schedin, Sophia; Dallner, Gustav.

In: Journal of Molecular Biology, Vol. 297, No. 3, 31.03.2000, p. 607-614.

Research output: Contribution to journalArticle

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