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KMID : 0356620140290020185
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Journal of Korean Society of Endocrinology
2014 Volume.29 No. 2 p.185 ~ p.194
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A Novel Cytosolic Isoform of Mitochondrial Trans-2-Enoyl-CoA Reductase Enhances Peroxisome Proliferator-Activated Receptor α Activity
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Kim Dong-Gyu
Yoo Jae-Cheal
Kim Eun-Ju
Lee Young-Sun
Yarishkin Oleg V.
Lee Da-Yong
Lee Kun-Ho
Hong Seong-Geun
Hwang Eun-Mi
Park Jae-Yong
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Abstract
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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.
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.
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KEYWORD
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Trans-2-enoyl-CoA reductase (NADPH), Cytosolic mitochondrial trans-2-enoyl-CoA reductase, PPAR alpha, Alternative splicing, Mitochondrial targeting sequences
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