Commentary on Distinct, but Previously Confused, Nrf1 Transcription Factors and Their Functions in Redox Regulation

Zhu, Yanhua; Xiang, Yuancai; L’honoré, Aurore; Montarras, Didier; Buckingham, Margaret; Zhang, Yiguo

doi:10.1016/j.devcel.2020.04.022

Cited by 4 publications

(3 citation statements)

References 7 publications

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“…To gain an insight into the underlying mechanism for mitochondrial dysfunction caused by loss of Nrf1α –∕– , we here examined the constitutive expression of two nuclear respiratory factors αPal NRF1 and GABPα NRF2 [ 38 , 39 ], cofactor PGC1α, and critical target genes (responsible for mitochondrial DNA replication and transcription, ETC/OXPHOS gene expression, and mitochondrial biogenesis [ 40 ]). The results showed that basal mRNA expression levels of αPal NRF1 , GABPα NRF2 and co-targeting mitochondrial transcription factors TFAM (transcription factor A, mitochondrial), TFB1M (transcription factor B1, mitochondrial) and TFB2M (transcription factor B2, mitochondrial), together with PGC1α , but not PGC1ß , were down-regulated, though to different extents, in Nrf1α –∕– cells ( Fig.…”

Section: Resultsmentioning

confidence: 99%

Nrf1 is an indispensable redox-determining factor for mitochondrial homeostasis by integrating multi-hierarchical regulatory networks

Feng

Wang

et al. 2022

Redox Biology

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Section: Resultsmentioning

confidence: 99%

Nrf1 is an indispensable redox-determining factor for mitochondrial homeostasis by integrating multi-hierarchical regulatory networks

Feng

Wang

et al. 2022

Redox Biology

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“…To gain an insight into the underlying mechanism for mitochondrial dysfunction caused by loss of Nrf1α –/– , we here examined the constitutive expression of two nuclear respiratory factors αPal NRF1 and GABPα NRF2 (45,46), cofactor PGC1α, and critical target genes [responsible for mitochondrial DNA replication and transcription, ETC/OXPHOS gene expression, and mitochondrial biogenesis (47)]. The results showed that basal mRNA expression levels of αPal NRF1 , GABPα NRF2 and co-targeting mitochondrial transcription factors TFAM, TFB1M and TFB2M , together with PGC1α , but not PGC1ß , were obviously down-regulated, though to different extents, in Nrf1α –/– cells (Figure 3A).…”

Section: Resultsmentioning

confidence: 99%

Nrf1 is an indispensable redox-determining factor for mitochondrial homeostasis by integrating multi-hierarchical regulatory networks

Feng

Wang

et al. 2022

Preprint

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To defend a vast variety of challenges in the oxygenated environments, all life forms have been evolutionally established a set of antioxidant, detoxification and cytoprotective systems during natural selection and adaptive survival, in order to maintain cell redox homeostasis and organ integrity in the healthy development and growth. Such antioxidant defense systems are predominantly regulated by two key transcription factors Nrf1 and Nrf2, but the underlying mechanism(s) for their coordinated redox control remains elusive. Here, we found that loss of full-length Nrf1 led to a dramatic increase in reactive oxygen species (ROS) and oxidative damages in Nrf1-/- cells, and this increase was not eliminated by drastic elevation of Nrf2, even though the antioxidant systems were also substantially enhanced by hyperactive Nrf2. Further studies revealed that the increased ROS production in Nrf1-/- resulted from a striking impairment in the mitochondrial oxidative respiratory chain and its gene expression regulated by nuclear respiratory factors, called aPalNRF1 and GABPNRF2. In addition to antioxidant capacity of cells, glycolysis was greatly augmented by aberrantly-elevated Nrf2, so to partially relieve the cellular energy demands, but aggravate its mitochondrial stress. The generation of ROS was also differentially regulated by Nrf1 and Nrf2 through miR-195 and/or mIR-497-mediated UCP2 pathway. Consequently, the epithelial-mesenchymal transformation (EMT) of Nrf1-/- cells was activated by putative ROS-stimulated signaling via MAPK, HIF1α, NF-kB, PI3K and AKT, all players involved in cancer development and progression. Taken together, it is inferable that Nrf1 acts as a potent integrator of redox regulation by multi-hierarchical networks.

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“…This confusion has been documented in the literature, e.g., see ''Commentary on Distinct, but Previously Confused, Nrf1 Transcription Factors and Their Functions in Redox Regulation.'' 23 The use of the NRF1 symbol to refer to both genes is unfortunate because NFE2L1 can regulate NRF1 in coordination with TFAM (HGNC: 11741; MIM: 600438), and both NFE2L1 and NRF1 are upregulated by PITX2 (HGNC: 9005; MIM: 601542). In cases like these where there has been past confusion, we would recommend inclusion of the HGNC ID to make it absolutely clear which gene is being referred to; for example, NRF1 (HGNC: 7996) and NFE2L1 (HGNC: 7781).…”

Section: Nrf1 and Nfe2l1mentioning

confidence: 99%

The risks of using unapproved gene symbols

Braschi

Seal

Jones

et al. 2021

The American Journal of Human Genetics

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Commentary on Distinct, but Previously Confused, Nrf1 Transcription Factors and Their Functions in Redox Regulation

Cited by 4 publications

References 7 publications

Nrf1 is an indispensable redox-determining factor for mitochondrial homeostasis by integrating multi-hierarchical regulatory networks

Nrf1 is an indispensable redox-determining factor for mitochondrial homeostasis by integrating multi-hierarchical regulatory networks

Nrf1 is an indispensable redox-determining factor for mitochondrial homeostasis by integrating multi-hierarchical regulatory networks

The risks of using unapproved gene symbols

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