A novel cytosolic isoform of mitochondrial trans-2-enoyl-CoA reductase enhances peroxisome proliferator-activated receptor a activity

Dong Gyu Kim, Jae Cheal Yoo, Eunju Kim, Young Sun Lee, Oleg V. Yarishkin, Da Yong Lee, Kun Ho Lee, Seong Geun Hong, Eun Mi Hwang, Jae-Yong Park

Research output: Contribution to journalArticle

11 Citations (Scopus)

Abstract

Background: Mitochondrial trans-2-enoyl-CoA reductase (MECR) is involved in mitochondrial synthesis of fatty acids and is highly expressed in mitochondria. MECR is also known as nuclear receptor binding factor-1, which was originally reported with yeast two-hybrid screening as a binding protein of the nuclear hormone receptor peroxisome proliferator-activated receptor a (PPARα). However, MECR and PPARα are localized at different compartment, mitochondria, and the nucleus, respectively. Therefore, the presence of a cytosolic or nuclear isoform of MECR is necessary for functional interaction between MECR and PPARα. Methods: To identify the expression pattern of MECR and the cytosolic form of MECR (cMECR), we performed reverse transcription polymerase chain reaction (RT-PCR) with various tissue samples from Sprague-Dawley rats. To confirm the interaction between cMECR and PPARα, we performed several binding assays such as yeast two-hybrid, coimmunoprecipitation, and bimolecular fluorescence complementation. To observe subcellular localization of these proteins, immunocytochemistry was performed. A luciferase assay was used to measure PPARα activity. Results: We provide evidence of an alternatively spliced variant of the rat MECR gene that yields cMECR. The cMECR lacks the N-terminal 76 amino acids of MECR and shows uniform distribution in the cytoplasm and nucleus of HeLa cells. cMECR directly bound PPARα in the nucleus and increased PPARα-dependent luciferase activity in HeLa cells. Conclusion: We found the cytosolic form of MECR (cMECR) was expressed in the cytosolic and/or nuclear region, directly binds with PPARα, and enhances PPARα activity.

Original languageEnglish
Pages (from-to)185-194
Number of pages10
JournalEndocrinology and Metabolism
Volume29
Issue number2
DOIs
Publication statusPublished - 2014 Jan 1
Externally publishedYes

Keywords

  • Alternative splicing
  • Cytosolic mitochondrial trans-2-enoyl-CoA reductase
  • Mitochondrial targeting sequences
  • PPAR alpha
  • Trans-2-enoyl-CoA reductase (NADPH)

ASJC Scopus subject areas

  • Endocrinology, Diabetes and Metabolism
  • Endocrinology

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