Nrf1 acts as a highly-conserved determinon for maintaining robust redox homeostasis in the eco-evo-devo process of life histories
Differential and even opposing functions of two major antioxidant transcription factors Nrf1 and Nrf2 (encoded by Nfe2l1 and Nfe2l2, respectively) are determined by distinctions in their tempospatial positioning, topological repartitioning, proteolytic processing, and biochemical modification, as we...
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Shared Science Publishers OG
2025-07-01
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| Series: | Cell Stress |
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| Online Access: | http://microbialcell.com/researcharticles/2025a-zhang-cell-stress |
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| author | Yiguo Zhang Xi Chen Meng Wang Yuping Zhu Wei Shi Chao Li Zhengwen Zhang Hiroaki Taniguchi Ping Ao |
| author_facet | Yiguo Zhang Xi Chen Meng Wang Yuping Zhu Wei Shi Chao Li Zhengwen Zhang Hiroaki Taniguchi Ping Ao |
| author_sort | Yiguo Zhang |
| collection | DOAJ |
| description | Differential and even opposing functions of two major antioxidant transcription factors Nrf1 and Nrf2 (encoded by Nfe2l1 and Nfe2l2, respectively) are determined by distinctions in their tempospatial positioning, topological repartitioning, proteolytic processing, and biochemical modification, as well as in their shared evolutionary origin. As a matter of fact, the allelopathic potentials of Nrf1 and Nrf2 (both resembling two entangled ‘Yin-Yang’ quanta that comply with a dialectic law of the unity of opposites) are fulfilled to coordinately control redox physiological homeostasis so as to be maintained within the presetting thresholds. By putative exponential curves of redox stress and intrinsic anti-redox capability, there is inferable to exist a set point at approaching zero with the ‘Golden Mean’ for the healthy survival (i.e., dubbed the ‘zero theory’). A bulk of the hitherto accumulating evidence demonstrates that the set point of redox homeostasis is dictated selectively by multi-hierarchical threshold settings, in which the living fossil-like Nrf1 acts as a robust indispensable determinon, whereas Nrf2 serves as a versatile chameleon-like master regulon, in governing the redox homeodynamic ranges. This is attributable to the facts that Nrf2 has exerted certain ‘double-edged sword’ effects on life process, whereas Nrf1 executes its essential physiobiological functions, along with unique pathophysiological phenotypes, by integrating its ‘three-in-one’ roles elicited as a specific triplet of direct sensor, transducer and effector within multi-hierarchical stress responsive signaling to redox metabolism and target gene reprogramming. Here, we also critically reviewed redox regulation of physio-pathological functions from the eco-evo-devo perspectives, through those coding rules (redox code, stress-coping code, and topogenetic code). The evolving concepts on stress and redox stress were also further revisited by scientific principles of physics and chemistry. Besides, several novel concepts such as oncoprotists, Reverse Central Dogma, and Grand Redox-Unifying Theory’ (GRUT) of life, together with diffusive reactive species (DRS)-based murburn concept integrating all stochastic electron-, proton- and/or moiety-transfer reactive and interactive processes (e.g., PCHEMS), are introduced in this interdisciplinary and synthetic review. |
| format | Article |
| id | doaj-art-8212e4e3c67548c0af56bafcebf9f9d1 |
| institution | Kabale University |
| issn | 2523-0204 |
| language | English |
| publishDate | 2025-07-01 |
| publisher | Shared Science Publishers OG |
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| series | Cell Stress |
| spelling | doaj-art-8212e4e3c67548c0af56bafcebf9f9d12025-08-20T03:50:02ZengShared Science Publishers OGCell Stress2523-02042025-07-0196514210.15698/cst2025.07.306Nrf1 acts as a highly-conserved determinon for maintaining robust redox homeostasis in the eco-evo-devo process of life historiesYiguo Zhang0Xi Chen1Meng Wang2Yuping Zhu3Wei Shi4Chao Li5Zhengwen Zhang6Hiroaki Taniguchi7Ping Ao8The Laboratory of Cell Biochemistry and Topogenetic Regulation, College of Bioengineering and Faculty of Medical Sciences, Chongqing University, No. 174 Shazheng Street, Shapingba District, Chongqing 400044, China.The Laboratory of Cell Biochemistry and Topogenetic Regulation, College of Bioengineering and Faculty of Medical Sciences, Chongqing University, No. 174 Shazheng Street, Shapingba District, Chongqing 400044, China.The Laboratory of Cell Biochemistry and Topogenetic Regulation, College of Bioengineering and Faculty of Medical Sciences, Chongqing University, No. 174 Shazheng Street, Shapingba District, Chongqing 400044, China.The Laboratory of Cell Biochemistry and Topogenetic Regulation, College of Bioengineering and Faculty of Medical Sciences, Chongqing University, No. 174 Shazheng Street, Shapingba District, Chongqing 400044, China.State Key Laboratory of Oil and Gas Reservoir Geology and Exploitation & Institute of Sedimentary Geology, Chengdu University of Technology, Chengdu 610059, China.State Key Laboratory of Oil and Gas Reservoir Geology and Exploitation & Institute of Sedimentary Geology, Chengdu University of Technology, Chengdu 610059, China.Laboratory of Neuroscience, Institute of Cognitive Neuroscience and School of Pharmacy, University College London, 29-39 Brunswick Square, London WC1N 1AX, England, United Kingdom.Department of Experimental Embryology, Institute of Genetics and Animal Biotechnology, Polish Academy of Sciences, 05-552 Jastrzebiec, Poland.College of Biomedical Engineering, Sichuan University, Chengdu, Sichuan 610044, China.Differential and even opposing functions of two major antioxidant transcription factors Nrf1 and Nrf2 (encoded by Nfe2l1 and Nfe2l2, respectively) are determined by distinctions in their tempospatial positioning, topological repartitioning, proteolytic processing, and biochemical modification, as well as in their shared evolutionary origin. As a matter of fact, the allelopathic potentials of Nrf1 and Nrf2 (both resembling two entangled ‘Yin-Yang’ quanta that comply with a dialectic law of the unity of opposites) are fulfilled to coordinately control redox physiological homeostasis so as to be maintained within the presetting thresholds. By putative exponential curves of redox stress and intrinsic anti-redox capability, there is inferable to exist a set point at approaching zero with the ‘Golden Mean’ for the healthy survival (i.e., dubbed the ‘zero theory’). A bulk of the hitherto accumulating evidence demonstrates that the set point of redox homeostasis is dictated selectively by multi-hierarchical threshold settings, in which the living fossil-like Nrf1 acts as a robust indispensable determinon, whereas Nrf2 serves as a versatile chameleon-like master regulon, in governing the redox homeodynamic ranges. This is attributable to the facts that Nrf2 has exerted certain ‘double-edged sword’ effects on life process, whereas Nrf1 executes its essential physiobiological functions, along with unique pathophysiological phenotypes, by integrating its ‘three-in-one’ roles elicited as a specific triplet of direct sensor, transducer and effector within multi-hierarchical stress responsive signaling to redox metabolism and target gene reprogramming. Here, we also critically reviewed redox regulation of physio-pathological functions from the eco-evo-devo perspectives, through those coding rules (redox code, stress-coping code, and topogenetic code). The evolving concepts on stress and redox stress were also further revisited by scientific principles of physics and chemistry. Besides, several novel concepts such as oncoprotists, Reverse Central Dogma, and Grand Redox-Unifying Theory’ (GRUT) of life, together with diffusive reactive species (DRS)-based murburn concept integrating all stochastic electron-, proton- and/or moiety-transfer reactive and interactive processes (e.g., PCHEMS), are introduced in this interdisciplinary and synthetic review.http://microbialcell.com/researcharticles/2025a-zhang-cell-stressnrf1nrf2homeostasisdeterminonregulontopogeneticsredox stresseco-evo-devoredox codestress-coping codeoncoprotist‘zero theory’reverse central dogmagrand redox-unifying theory (grut)murburn concept |
| spellingShingle | Yiguo Zhang Xi Chen Meng Wang Yuping Zhu Wei Shi Chao Li Zhengwen Zhang Hiroaki Taniguchi Ping Ao Nrf1 acts as a highly-conserved determinon for maintaining robust redox homeostasis in the eco-evo-devo process of life histories Cell Stress nrf1 nrf2 homeostasis determinon regulon topogenetics redox stress eco-evo-devo redox code stress-coping code oncoprotist ‘zero theory’ reverse central dogma grand redox-unifying theory (grut) murburn concept |
| title | Nrf1 acts as a highly-conserved determinon for maintaining robust redox homeostasis in the eco-evo-devo process of life histories |
| title_full | Nrf1 acts as a highly-conserved determinon for maintaining robust redox homeostasis in the eco-evo-devo process of life histories |
| title_fullStr | Nrf1 acts as a highly-conserved determinon for maintaining robust redox homeostasis in the eco-evo-devo process of life histories |
| title_full_unstemmed | Nrf1 acts as a highly-conserved determinon for maintaining robust redox homeostasis in the eco-evo-devo process of life histories |
| title_short | Nrf1 acts as a highly-conserved determinon for maintaining robust redox homeostasis in the eco-evo-devo process of life histories |
| title_sort | nrf1 acts as a highly conserved determinon for maintaining robust redox homeostasis in the eco evo devo process of life histories |
| topic | nrf1 nrf2 homeostasis determinon regulon topogenetics redox stress eco-evo-devo redox code stress-coping code oncoprotist ‘zero theory’ reverse central dogma grand redox-unifying theory (grut) murburn concept |
| url | http://microbialcell.com/researcharticles/2025a-zhang-cell-stress |
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