title: A Novel Cytosolic Isoform of Mitochondrial Trans-2-Enoyl-CoA Reductase Enhances Peroxisome Proliferator-Activated Receptor α Activity.
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 α (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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Physiology, Institute of Health Science, Medical Research Center for Neural Dysfunction, Gyeongsang National University School of Medicine, Jinju, Korea.
authors.forename: Dong-Gyu
authors.initials: DG
authors.lastname: Kim
authors.affiliation: Department of Physiology, Institute of Health Science, Medical Research Center for Neural Dysfunction, Gyeongsang National University School of Medicine, Jinju, Korea.
authors.forename: Jae Cheal
authors.initials: JC
authors.lastname: Yoo
authors.affiliation: Center for Functional Connectomics, Korea Institute of Science and Technology, Seoul, Korea.
authors.forename: Eunju
authors.initials: E
authors.lastname: Kim
authors.affiliation: Department of Physiology, Institute of Health Science, Medical Research Center for Neural Dysfunction, Gyeongsang National University School of Medicine, Jinju, Korea.
authors.forename: Young-Sun
authors.initials: YS
authors.lastname: Lee
authors.affiliation: Center for Functional Connectomics, Korea Institute of Science and Technology, Seoul, Korea.
authors.forename: Oleg V
authors.initials: OV
authors.lastname: Yarishkin
authors.affiliation: Center for Functional Connectomics, Korea Institute of Science and Technology, Seoul, Korea.
authors.forename: Da Yong
authors.initials: DY
authors.lastname: Lee
authors.affiliation: Department of Marine Life Science, Chosun University College of Natural Sciences, Gwangju, Korea.
authors.forename: Kun Ho
authors.initials: KH
authors.lastname: Lee
authors.affiliation: Department of Physiology, Institute of Health Science, Medical Research Center for Neural Dysfunction, Gyeongsang National University School of Medicine, Jinju, Korea.
authors.forename: Seong-Geun
authors.initials: SG
authors.lastname: Hong
authors.affiliation: Center for Functional Connectomics, Korea Institute of Science and Technology, Seoul, Korea.
authors.forename: Eun Mi
authors.initials: EM
authors.lastname: Hwang
authors.affiliation: Department of Physiology, Institute of Health Science, Medical Research Center for Neural Dysfunction, Gyeongsang National University School of Medicine, Jinju, Korea. ; Center for Functional Connectomics, Korea Institute of Science and Technology, Seoul, Korea.
authors.forename: Jae-Yong
authors.initials: JY
authors.lastname: Park
keywords: Alternative splicing; Cytosolic mitochondrial trans-2-enoyl-CoA reductase; Mitochondrial targeting sequences; PPAR alpha; Trans-2-enoyl-CoA reductase (NADPH)