Journal
GENE
Volume 374, Issue -, Pages 39-49Publisher
ELSEVIER SCIENCE BV
DOI: 10.1016/j.gene.2006.01.009
Keywords
GABP; mitochondria; RNA interference; transcription factor; transcriptional regulation
Categories
Funding
- NEI NIH HHS [R01 EY05439] Funding Source: Medline
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Cytochrome c oxidase (COX), the terminal enzyme of the electron transport chain, is a bigenomic enzyme with 13 subunits. The mechanism coordinating the transcription of these subunits is poorly understood. We investigated the role of nuclear respiratory factor-2 (NRF-2) in intragenomic regulation of nuclear COX genes. Vector-mediated short-hairpin RNA interference against NRF-2 alpha reduced all 10 COX nuclear subunit mRNAs and mRNAs of other genes involved in mitochondrial function/biogenesis. NPF-2 binding site was necessary for the rat COX 4il promoter to down-regulate in response to decreased energy demands in primary neurons. Over-expression of NRF-2 protein prevented the down-regulation of transcriptional activity by TTX. Finally, NRF-2 binding sites in isolation were sufficient for modulating COX subunit 4il and 6A1 promoters' activity in response to decreased energy demand. These results indicate that NRF-2 is a vital part of a molecular mechanism that senses upstream energy signals and modulates COX transcriptional levels in mammalian cells. (c) 2006 Elsevier B.V. All rights reserved.
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