Chapter 2 Regulation of Mitochondrial Functions by Transcription Factor NRF 2

V. Natarajan, N.L. Parinandi (eds.), Mitochondrial Function in Lung Health and Disease, Respiratory Medicine 15, DOI 10.1007/978-1-4939-0829-5_2, © Springer Science+Business Media New York 2014 Abstract Protective and adaptive responses initiated by lung-resident and infi ltrated cells play an important role in mitigating the detrimental effects of various toxicants. However, the development of a variety of pulmonary diseases has been attributed to a dysfunctional cellular response following acute or chronic toxicant exposure, resulting from altered gene expression. Although mitochondria have been long thought as cellular powerhouses and regulators of bioenergetics, their biogenesis is promoted by diverse patho-physiological stimuli including cell division, development, exercise, postnatal breathing, metabolism, oxidative stress, and infl ammation. Emerging evidence strongly supports the idea that mitochondrial dysfunction caused by various toxicants and pro-oxidants is the origin of pathogenesis and ultimately results in morbidity and mortality. The transcriptional factor nuclear factor (erythroid-derived 2)-like 2 (Nfe2l2 or NRF2), by binding to the antioxidant response element (ARE) of the promoters of redox-sensitive genes, induces the expression of cytoprotective and antioxidative proteins that play a crucial role in mitigating the cellular stress and damage caused by pro-infl ammatory and oxidant stimuli. Depending on the extent of its activation, redox signaling can promote either benefi cial stress-resolving mitochondrial activity or mitochondrial dysfunction. Accumulating evidence suggests that a defi ciency of NRF2 causes mitochondrial dysfunction, culminating in severe lung injury and infl ammation. This review Chapter 2 Regulation of Mitochondrial Functions by Transcription Factor NRF2