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. 2003 Jan 31;278(5):2963-8.
doi: 10.1074/jbc.M209995200. Epub 2002 Nov 13.

NF-kappa B and I kappa B alpha are found in the mitochondria. Evidence for regulation of mitochondrial gene expression by NF-kappa B

Patricia C Cogswell  1 , David F Kashatus, Jayne A Keifer, Denis C Guttridge, Julie Y Reuther, Cindy Bristow, Sophie Roy, Donald W Nicholson, Albert S Baldwin Jr
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Free article

NF-kappa B and I kappa B alpha are found in the mitochondria. Evidence for regulation of mitochondrial gene expression by NF-kappa B

Patricia C Cogswell et al. J Biol Chem. .
Free article

Abstract

The transcription factor NF-kappa B has been shown to be predominantly cytoplasmically localized in the absence of an inductive signal. Stimulation of cells with inflammatory cytokines such as tumor necrosis factor alpha or interleukin-1 induces the degradation of I kappa B, the inhibitor of NF-kappa B, allowing nuclear accumulation of NF-kappa B and regulation of specific gene expression. The degradation of I kappa B is controlled initially by phosphorylation induced by the I kappa B kinase, which leads to ubiquitination and subsequent proteolysis of the inhibitor by the proteasome. We report here that NF-kappa B and I kappa B alpha (but not I kappa B beta) are also localized in the mitochondria. Stimulation of cells with tumor necrosis factor alpha leads to the phosphorylation of mitochondrial I kappa B alpha and its subsequent degradation by a nonproteasome-dependent pathway. Interestingly, expression of the mitochondrially encoded cytochrome c oxidase III and cytochrome b mRNAs were reduced by cytokine treatment of cells. Inhibition of activation of mitochondrial NF-kappa B by expression of the superrepressor form of I kappa B alpha inhibited the loss of expression of both cytochrome c oxidase III and cytochrome b mRNA. These data indicate that the NF-kappa B regulatory pathway exists in mitochondria and that NF-kappa B can negatively regulate mitochondrial mRNA expression.

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