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 journalArticlepeer-review

12 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

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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