![]() The NF-κB signaling pathway links pathogenic signals and cellular danger signals thus organizing cellular resistance to invading pathogens. Nuclear factor kappa B (NF-κB) is an ancient protein transcription factor ( Salminen et al., 2008) and considered a regulator of innate immunity ( Baltimore, 2009). Also, the data associated with the mitochondrial localization of proteins must be yet further proved with additional experiments. The discussion at times is speculative and perhaps even provocative to some, since NF-κB does not yet have defined mitochondrial targeting sequences for some nuclear-encoded mitochondrial genes and mechanisms of mitochondrial import for NF-κB are not yet entirely understood. In this review, an attempt is made to understand how NF-κB activity contributes to overall mitochondrial function – both inside and out. Therefore, it is essential to understand the complexity of these roles both inside and out of this organelle. Studies also show NF-κB can influence mitochondrial function from outside the mitochondria. Both are ancient in their appearance in our biological record where both contribute substantially to cell survival, cell death, and the regulation of function and/or disease. Upon further thought the lack of studies on NF-κB activity in mitochondrial function is surprising given the importance and the evolutionary history of both NF-κB and the mitochondrion. For example, in 2001 it was first published that NF-κB subunits were found in the mitochondria, including not only IkBα and NF-κB p65 subunits, but also NF-κB pathway proteins such as IKKα, IKKβ, and IKKγ, but not much follow-up work has been done to date. However, studies on NF-κB activity in mitochondrial function are much more limited and scattered throughout the literature. 2Department of Pharmacology and Therapeutics, Max Rady College of Medicine, University of Manitoba, Winnipeg, MB, CanadaĪ large body of literature supports the idea that nuclear factor kappa B (NF-κB) signaling contributes to not only immunity, but also inflammation, cancer, and nervous system function.Boniface Hospital Research, Winnipeg, MB, Canada 1Division of Neurodegenerative Disorders, St.
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