Faculty Collaboration Database

Nuclear respiratory factor 2 senses changing cellular energy demands and its silencing down-regulates cytochrome oxidase and other target gene mRNAs. Gene 2006 Jun 07;374:39-49

Date

03/07/2006

Pubmed ID

16516409

DOI

10.1016/j.gene.2006.01.009

Scopus ID

2-s2.0-33646690296 (requires institutional sign-in at Scopus site)   92 Citations

Abstract

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-2alpha reduced all 10 COX nuclear subunit mRNAs and mRNAs of other genes involved in mitochondrial function/biogenesis. NRF-2 binding site was necessary for the rat COX 4i1 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 4i1 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.

Author List

Ongwijitwat S, Liang HL, Graboyes EM, Wong-Riley MT

MESH terms used to index this publication - Major topics in bold

Animals
Animals, Newborn
Binding Sites
Cells, Cultured
Cerebral Cortex
Down-Regulation
Electron Transport Complex IV
Energy Metabolism
Gene Expression Regulation, Enzymologic
Gene Silencing
Genetic Vectors
Mice
NIH 3T3 Cells
Neurons
Nuclear Respiratory Factors
Promoter Regions, Genetic
Protein Binding
RNA Interference
RNA, Messenger
RNA, Small Interfering
Rats
Tetrodotoxin
Transcription, Genetic