What is the Difference Between NRF1 and NRF2

The key difference between NRF1 and NRF2 is their function. NRF1 is a transcription factor that activates the expression of some important metabolic genes that regulate cellular growth and nuclear genes required for respiration, heme biosynthesis, mitochondrial DNA transcription, and replication, while NRF2 is a transcription factor that regulates the expression of antioxidant genes that protect against oxidative damage triggered by injury and inflammation.

Transcription factors are protein molecules involved in controlling the rate of transcription of genetic information from DNA to messenger RNA (mRNA). Therefore, the key function of transcription factors is to regulate tuning on and off the genes in order to make sure the genes are expressed correctly at the right time throughout the life cycle of the organism. NRF1 and NRF2 are two important human transcription factors that control the expression of important genes.

CONTENTS

1. Overview and Key Difference
2. What is NRF1  
3. What is NRF2
4. Similarities – NRF1 and NRF2
5. NRF1 vs NRF2 in Tabular Form
6. Summary – NRF1 vs NRF2

What is NRF1 (Nuclear Respiratory Factor 1)?

Nuclear respiratory factor 1 (NRF1) is a transcription factor that activates the expression of some important metabolic genes, regulating cellular growth and nuclear genes required for respiration, heme biosynthesis, mitochondrial DNA transcription, and replication. NRF1, together with NRF2, mediates the genomic coordination between nuclear and mitochondrial genes. This is done by directly regulating the expression of several nuclear-encoded ETC proteins and indirectly regulating three mitochondrial-encoded genes through activating mtTFA, mtTFB1, and mtTFB2.

It is also known as NRF-1. Moreover, this protein has also been associated with the regulation of neurite outgrowth. Neurite refers to any projection from the neuron cell body such as axon and dendrite. Furthermore, cyclinD1 dependent kinase coordinates nuclear DNA synthesis and mitochondrial function by phosphorylating NRF1 at the S47 position. In addition to that, NRFI has also been shown to interact with other important proteins such as DYNLL1, PPARGCIA, and PPRC1.

What is NRF2 (Factor Erythroid 2-Related Factor 2)?

Nuclear factor erythroid 2-related factor 2 (NRF2) is a transcription factor that regulates the expression of antioxidant genes, which protect against oxidative damage triggered by injury and inflammation. It is encoded by the NFE2L2 gene in humans. In vitro conditions, NRF2 binds to antioxidant response elements (AREs) in the nucleus, leading to the transcription of ARE genes. NRF2 also increases heme oxygenase 1 in vitro conditions involved in the healing process. Moreover, NRF2 also inhibits NLRP3 inflammasome that induces inflammatory responses.

Furthermore, NRF2 participates in complex regulatory pathways and performs a pleitropic function in the regulation of metabolism, inflammation, autophagy, proteostasis, mitochondrial physiology, and immune responses. Several drugs stimulate the NRF2 pathway. These drugs are studied for the treatment of diseases that are caused by oxidative stress. Examples of the drugs that induce the NRF2 pathway include dimethyl fumarate and dithiolethiones. Dimethyl fumarate is a drug used for the treatment of multiple sclerosis. Dithiolethiones inhibit cancer formation in rodent organs, including bladder, blood, colon, kidney, liver, lung, pancreas, stomach, trachea, skin, and mammary tissue. However, dithiolethiones are not approved for human usage due to toxicity such as neurotoxicity and gastrointestinal toxicity.

What are the Similarities Between NRF1 and NRF2?

• NRF1 and NRF2 are two important human transcription factors that control the expression of important genes.
• NRF1, together with NRF2, mediates the genomic coordination between nuclear and mitochondrial genes.
• Both are proteins.
• Their functions are extremely important for the survival of humans.

What is the Difference Between NRF1 and NRF2?

NRF1 is a transcription factor that activates the expression of some important metabolic genes, which regulate cell growth and nuclear genes required for respiration, heme biosynthesis, mitochondrial DNA transcription, and replication, while NRF2 is a transcription factor that regulates the expression of antioxidant genes, which protect against oxidative damage triggered by injury and inflammation. Thus, this is the key difference between NRF1 and NRF2. Furthermore, NRF1 is encoded by the NRF1 gene, while NRF2 is encoded by the NFE2L2 gene.

The below infographic presents the differences between NRF1 and NRF2 in tabular form for side by side comparison.

Summary – NRF1 vs NRF2

NRF1 and NRF2 are two human transcription factors. NRF1 is a transcription factor that activates the expression of some important metabolic genes regulating cellular growth and nuclear genes required for respiration, heme biosynthesis, mitochondrial DNA transcription, and replication while NRF2 is a transcription factor that regulates the expression of antioxidant genes, which protect against oxidative damage triggered by injury and inflammation. So, this summarizes the difference between NRF1 and NRF2.

Reference:

1. Ma, Qiang. “Role of NRF2 in Oxidative Stress and Toxicity.” Annual Review of Pharmacology and Toxicology, U.S. National Library of Medicine.
2. “NRF1.” An Overview | ScienceDirect Topics.

Image Courtesy:

1. “RI and CI alter molecular mechanisms determining survival” By Kiang, J.G., Olabisi, A.O. Radiation: a poly-traumatic hit leading to multi-organ injury. Cell Biosci 9, 25 (2019)  (CC BY 4.0) via Commons Wikimedia
2. “KEAP1 NRF2 signaling pathway” By Warren L. Wu and Thales Papagiannakopoulos – Annual Reviews (CC BY 4.0) via Commons Wikimedia