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Lookup NU author(s): Dr Iglika Ivanova, Professor Neil PerkinsORCiD
This work is licensed under a Creative Commons Attribution 4.0 International License (CC BY 4.0).
© 2019 The Author(s).The nuclear factor-κB (NF-κB) family of transcription factors can directly or indirectly regulate many important areas of biology, including immunity, inflammation and cell survival. One intriguing aspect of NF-κB crosstalk with other cell signalling pathways is its regulation of mitochondrial biology, including biogenesis, metabolism and apoptosis. In addition to regulating the expression of mitochondrial genes encoded in the nucleus, NF-κB signalling components are also found within mitochondria themselves and associated with mitochondrial DNA. However, complete biochemical analysis of mitochondrial and sub-mitochondrial localisation of all NF-κB subunits has not been undertaken. Here, we show that only the RelA NF-κB subunit and its inhibitor IκBα reside within mitochondria, whilst p50 is found in the endoplasmic reticulum (ER). Fractionation of mitochondria revealed that only RelA was found in the mitoplast, the location of the mtDNA. We demonstrate that hypoxia leads to a very rapid but transient accumulation of RelA and IκBα in mitochondria. This effect required reactive oxygen species (ROS) but was not dependent on the hypoxia sensing transcription factor subunit HIF1α or intracellular Ca2+ release. We also observed rapid mitochondrial localisation of transcription factor STAT3 following hypoxia. Inhibition of STAT3 blocked RelA and IκBα mitochondrial localisation revealing a previously unknown aspect of crosstalk between these key cellular regulators.
Author(s): Ivanova IG, Perkins ND
Publication type: Article
Publication status: Published
Journal: Bioscience Reports
Year: 2019
Volume: 39
Issue: 9
Print publication date: 16/09/2019
Online publication date: 04/09/2019
Acceptance date: 21/08/2019
Date deposited: 01/10/2019
ISSN (print): 0144-8463
ISSN (electronic): 1573-4935
Publisher: Portland Press Ltd
URL: https://doi.org/10.1042/BSR20192101
DOI: 10.1042/BSR20192101
PubMed id: 31484794
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