Regulation of Mitochondrial Functions by Transcription Factor NRF2

  • Narsa M. Reddy
  • Wajiha Qureshi
  • Haranath Potteti
  • Dhananjaya V. Kalvakolanu
  • Sekhar P. ReddyEmail author
Part of the Respiratory Medicine book series (RM, volume 15)


Protective and adaptive responses initiated by lung-resident and infiltrated 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 inflammation. 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-inflammatory and oxidant stimuli. Depending on the extent of its activation, redox signaling can promote either beneficial stress-resolving mitochondrial activity or mitochondrial dysfunction. Accumulating evidence suggests that a deficiency of NRF2 causes mitochondrial dysfunction, culminating in severe lung injury and inflammation. This review discusses the biology and role of NRF2 in regulating mitochondrial functions and summarizes current strategies used to target NRF2 in order to confer protection against pulmonary disorders linked to mitochondrial dysfunction.


Autophagy Mitophagy Antioxidants Lung diseases KEAP1 ROS 



Alzheimer’s disease


Acute lung injury


Acute respiratory distress syndrome


Antioxidant response element


Autophagy gene




B-cell lymphoma


1-[2-Cyano-3,12-dioxooleana-1,9(11)-dien-28-oyl] imidazole


Carbon monoxide


Chronic obstructive pulmonary disease


Electron transport chain


Fas ligand


Glutamate cysteine ligase


Glutamate cysteine ligase catalytic subunit


Glutamate cysteine ligase modifier subunit


Glutathione peroxidase


Glutathione reductase




Glycogen synthase kinase 3β


Glutathione reductase


Glutathione disulfide


Glutathione transferase


Heme oxygenase1




Mitochondrial glutathione


Mitochondrial glutathione disulfide


Mitochondrial outer membrane permeabilization


Mitochondrial oxidative phosphorylation


Mitochondrial DNA


Mitochondrial estrogen receptor


Mitochondrial glucocorticoid


NAD(P)H:quinone oxidoreductase


Nuclear respiratory factor-1


Nuclear respiratory factor-2


Nuclear factor (erythroid-derived 2)-like 2


8-Oxoguanine DNA glycosylase 1


Parkinson’s disease


Mitochondrial phosphoglycerate mutase family member 5


Peroxisome proliferator-activated receptor gamma coactivator




Protein kinase B


Peroxisome proliferator-activated receptor




Nitrogen-based reactive nitrogen species


Reactive oxygen species


Superoxide dismutase




Mitochondrial transcription factor A


Tumor necrosis factor-alpha




Thioredoxin reductase



Supported by the NIH grants HL66109, ES11863, DK084445, and ES18998 and the Flight Attendant Medical Research Institute (FAMRI) (to SPR) and NIH grant CA78282 (to DVK).


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Copyright information

© Springer Science+Business Media New York 2014

Authors and Affiliations

  • Narsa M. Reddy
    • 1
  • Wajiha Qureshi
    • 1
  • Haranath Potteti
    • 1
  • Dhananjaya V. Kalvakolanu
    • 2
  • Sekhar P. Reddy
    • 3
    Email author
  1. 1.Department of PediatricsUniversity of Illinois at ChicagoChicagoUSA
  2. 2.Department of Microbiology and ImmunologyUniversity of MarylandBaltimoreUSA
  3. 3.Department of Pediatrics, College of MedicineUniversity of Illinois at ChicagoChicagoUSA

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