Involvement of retinoid X receptor α in coenzyme Q metabolism

Magnus Bentinger, Mikael Turunen, Xiao Xue Zhang, Yu-Jui Yvonne Wan, Gustav Dallner

Research output: Contribution to journalArticle

24 Citations (Scopus)

Abstract

The nuclear retinoid X receptor α (RXRα) is the heterodimer partner in several nuclear receptors, some of them regulating lipid biosynthesis. Since coenzyme Q (CoQ) levels are greatly modified in aging and a number of diseases, we have investigated the involvement of RXRα in the biosynthetic regulation of this lipid by using a hepatocyte-specific RXRα-deficient mouse strain (RXRα-def). In the receptor-deficient liver, the amount of CoQ decreased to half of the control, and it was demonstrated that this decrease was caused by a significantly lowered rate of biosynthesis. On the other hand, induction of CoQ was extensive in both control and RXRα-def liver using the peroxisomal inducer di(2-ethylhexyl)phthalate (DEHP). Since the RXRα deficiency was specific to liver, no change in CoQ content or biosynthesis was observed in kidney. The other mevalonate pathway lipids, cholesterol and dolichol, were unchanged in the RXRα-def liver. Upon treatment with DEHP, cholesterol decreased in the control but remained unchanged in the receptor-deficient mice. In control mice, cold exposure elevated CoQ levels by 60%, but this induction did not occur in the liver of RXRα-def mice. In contrast, PPARα-null mice, which lack induction upon treatment with peroxisomal inducers, respond to cold exposure and CoQ content is increased. The amount of cholesterol decreased in both control and RXRα-def liver upon cold treatment. The results demonstrate that RXRα is required for CoQ biosynthesis and for its induction upon cold treatment, but does not appear to be involved in the basic synthesis of cholesterol and dolichol. The receptor is not involved in the elevated CoQ biosynthesis during peroxisomal induction.

Original languageEnglish (US)
Pages (from-to)795-803
Number of pages9
JournalJournal of Molecular Biology
Volume326
Issue number3
DOIs
StatePublished - Feb 21 2003

Fingerprint

Retinoid X Receptors
Ubiquinone
Cholesterol
Dolichol
Liver
Lipids
Mevalonic Acid
Peroxisome Proliferator-Activated Receptors
Cytoplasmic and Nuclear Receptors
Hepatocytes

Keywords

  • Cholesterol
  • Coenzyme Q
  • Peroxisomal proliferators
  • PPARα
  • RXRα

ASJC Scopus subject areas

  • Virology

Cite this

Involvement of retinoid X receptor α in coenzyme Q metabolism. / Bentinger, Magnus; Turunen, Mikael; Zhang, Xiao Xue; Wan, Yu-Jui Yvonne; Dallner, Gustav.

In: Journal of Molecular Biology, Vol. 326, No. 3, 21.02.2003, p. 795-803.

Research output: Contribution to journalArticle

Bentinger, Magnus ; Turunen, Mikael ; Zhang, Xiao Xue ; Wan, Yu-Jui Yvonne ; Dallner, Gustav. / Involvement of retinoid X receptor α in coenzyme Q metabolism. In: Journal of Molecular Biology. 2003 ; Vol. 326, No. 3. pp. 795-803.
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