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Title: Negative transcriptional regulation of mitochondrial transcription factor A (TFAM) by nuclear TFAM

Abstract

Highlights: • TFAM localizes in nuclei and mitochondria of neuronal cells. • Nuclear TFAM does not bind the Tfam promoter. • Nuclear TFAM reduced the Tfam promoter activity via suppressing NRF-1 activity. • A novel self-negative feedback regulation of Tfam gene expression is explored. • FAM may play different roles depending on its subcellular localizations. - Abstract: The nuclear DNA-encoded mitochondrial transcription factor A (TFAM) is synthesized in cytoplasm and transported into mitochondria. TFAM enhances both transcription and replication of mitochondrial DNA. It is unclear, however, whether TFAM plays a role in regulating nuclear gene expression. Here, we demonstrated that TFAM was localized to the nucleus and mitochondria by immunostaining, subcellular fractionation, and TFAM-green fluorescent protein hybrid protein studies. In HT22 hippocampal neuronal cells, human TFAM (hTFAM) overexpression suppressed human Tfam promoter-mediated luciferase activity in a dose-dependent manner. The mitochondria targeting sequence-deficient hTFAM also repressed Tfam promoter activity to the same degree as hTFAM. It indicated that nuclear hTFAM suppressed Tfam expression without modulating mitochondrial activity. The repression required for nuclear respiratory factor-1 (NRF-1), but hTFAM did not bind to the NRF-1 binding site of its promoter. TFAM was co-immunoprecipitated with NRF-1. Taken together, we suggest that nuclear TFAM down-regulatemore » its own gene expression as a NRF-1 repressor, showing that TFAM may play different roles depending on its subcellular localizations.« less

Authors:
; ; ; ;
Publication Date:
OSTI Identifier:
22416621
Resource Type:
Journal Article
Resource Relation:
Journal Name: Biochemical and Biophysical Research Communications; Journal Volume: 450; Journal Issue: 1; Other Information: Copyright (c) 2014 Elsevier Science B.V., Amsterdam, The Netherlands, All rights reserved.; Country of input: International Atomic Energy Agency (IAEA)
Country of Publication:
United States
Language:
English
Subject:
60 APPLIED LIFE SCIENCES; CELL NUCLEI; CYTOPLASM; DNA; DOSES; FEEDBACK; FLUORESCENCE; FRACTIONATION; GENES; HUMAN POPULATIONS; HYBRIDIZATION; LUCIFERASE; MITOCHONDRIA; NERVE CELLS; PROMOTERS; TRANSCRIPTION; TRANSCRIPTION FACTORS

Citation Formats

Lee, Eun Jin, Kang, Young Cheol, Park, Wook-Ha, Jeong, Jae Hoon, and Pak, Youngmi Kim, E-mail: ykpak@khu.ac.kr. Negative transcriptional regulation of mitochondrial transcription factor A (TFAM) by nuclear TFAM. United States: N. p., 2014. Web. doi:10.1016/J.BBRC.2014.05.082.
Lee, Eun Jin, Kang, Young Cheol, Park, Wook-Ha, Jeong, Jae Hoon, & Pak, Youngmi Kim, E-mail: ykpak@khu.ac.kr. Negative transcriptional regulation of mitochondrial transcription factor A (TFAM) by nuclear TFAM. United States. doi:10.1016/J.BBRC.2014.05.082.
Lee, Eun Jin, Kang, Young Cheol, Park, Wook-Ha, Jeong, Jae Hoon, and Pak, Youngmi Kim, E-mail: ykpak@khu.ac.kr. Fri . "Negative transcriptional regulation of mitochondrial transcription factor A (TFAM) by nuclear TFAM". United States. doi:10.1016/J.BBRC.2014.05.082.
@article{osti_22416621,
title = {Negative transcriptional regulation of mitochondrial transcription factor A (TFAM) by nuclear TFAM},
author = {Lee, Eun Jin and Kang, Young Cheol and Park, Wook-Ha and Jeong, Jae Hoon and Pak, Youngmi Kim, E-mail: ykpak@khu.ac.kr},
abstractNote = {Highlights: • TFAM localizes in nuclei and mitochondria of neuronal cells. • Nuclear TFAM does not bind the Tfam promoter. • Nuclear TFAM reduced the Tfam promoter activity via suppressing NRF-1 activity. • A novel self-negative feedback regulation of Tfam gene expression is explored. • FAM may play different roles depending on its subcellular localizations. - Abstract: The nuclear DNA-encoded mitochondrial transcription factor A (TFAM) is synthesized in cytoplasm and transported into mitochondria. TFAM enhances both transcription and replication of mitochondrial DNA. It is unclear, however, whether TFAM plays a role in regulating nuclear gene expression. Here, we demonstrated that TFAM was localized to the nucleus and mitochondria by immunostaining, subcellular fractionation, and TFAM-green fluorescent protein hybrid protein studies. In HT22 hippocampal neuronal cells, human TFAM (hTFAM) overexpression suppressed human Tfam promoter-mediated luciferase activity in a dose-dependent manner. The mitochondria targeting sequence-deficient hTFAM also repressed Tfam promoter activity to the same degree as hTFAM. It indicated that nuclear hTFAM suppressed Tfam expression without modulating mitochondrial activity. The repression required for nuclear respiratory factor-1 (NRF-1), but hTFAM did not bind to the NRF-1 binding site of its promoter. TFAM was co-immunoprecipitated with NRF-1. Taken together, we suggest that nuclear TFAM down-regulate its own gene expression as a NRF-1 repressor, showing that TFAM may play different roles depending on its subcellular localizations.},
doi = {10.1016/J.BBRC.2014.05.082},
journal = {Biochemical and Biophysical Research Communications},
number = 1,
volume = 450,
place = {United States},
year = {Fri Jul 18 00:00:00 EDT 2014},
month = {Fri Jul 18 00:00:00 EDT 2014}
}