Related Experiment Video
Updated: Feb 11, 2026
12:07
Profiling Thiol Redox Proteome Using Isotope Tagging Mass Spectrometry
Published on: March 24, 2012
16.7K
The KEAP1-NRF2 System: a Thiol-Based Sensor-Effector Apparatus for Maintaining Redox Homeostasis
Masayuki Yamamoto1, Thomas W Kensler1, Hozumi Motohashi1
1Department of Medical Biochemistry, Graduate School of Medicine, Tohoku University , Sendai , Japan ; Department of Pharmacology & Chemical Biology, University of Pittsburgh , Pittsburgh, Pennsylvania ; and Department of Gene Expression Regulation, Institute of Development, Aging and Cancer, Tohoku University , Sendai , Japan.
Physiological Reviews
|May 3, 2018
Summary
The Kelch-like ECH-associated protein 1-NF-E2-related factor 2 (KEAP1-NRF2) system protects cells from stress. Harnessing this system may be key to healthy aging and treating diseases.
Area of Science:
- Cellular biology
- Molecular biology
- Biochemistry
Background:
- The KEAP1-NRF2 system is central to cellular defense against oxidative and electrophilic stress.
- KEAP1 senses redox insults, while NRF2 regulates cytoprotective genes.
- KEAP1 normally represses NRF2, but stress liberates NRF2.
Purpose of the Study:
- To review the KEAP1-NRF2 system's historical milestones and molecular mechanisms.
- To provide a comprehensive overview of KEAP1 and NRF2 functions in physiology and pathology.
- To highlight the KEAP1-NRF2 system's clinical significance as a therapeutic target.
Main Methods:
- Literature review of historical studies on KEAP1-NRF2.
- Analysis of molecular mechanisms governing KEAP1 and NRF2 functions.
- Examination of KEAP1-NRF2 roles in various biological processes and diseases.
Main Results:
- The KEAP1-NRF2 system's rapid inducibility via derepression is a key feature.
- KEAP1-NRF2 is involved in cell proliferation, differentiation, and cytoprotection.
- Dysregulation of KEAP1-NRF2 is implicated in aging-related disorders.
Conclusions:
- Understanding KEAP1-NRF2 molecular mechanisms is crucial for its therapeutic application.
- Targeting the KEAP1-NRF2 system offers potential for disease prevention and treatment.
- Controlled manipulation of KEAP1-NRF2 is vital for promoting healthy aging and human well-being.
Related Concept Videos
02:58Balancing Redox Equations
62.3K
Electrochemistry is the science involved in the interconversion of electrical and chemical reactions. Such reactions are called reduction-oxidation, or redox reactions. These important reactions are defined by changes in oxidation states for one or more reactant elements and include a subset of reactions involving the transfer of electrons between reactant species. Electrochemistry as a field has evolved to yield sufficient insights on the fundamental principles of redox chemistry and multiple...
62.3K
01:24Redox Reactions
58.9K
Oxidation-reduction or redox reactions involve the transfer of electrons from one molecule or atom to another. When an atom gains an electron, another atom must lose an electron, meaning oxidation and reduction must occur together. Since the redox occurs in pairs, the atom that gets oxidized is also called the reducing agent or reductant, and the atom that is reduced is also called the oxidizing agent or oxidant. A straightforward way to remember the definitions of oxidation and reduction is...
58.9K
01:27Redox Reactions
1.1K
Redox reactions are vital biochemical processes that underpin energy metabolism in cells. These reactions involve the transfer of electrons between molecules, occurring in tandem as oxidation and reduction. Oxidation refers to the loss of electrons, while reduction denotes their gain. This coupling ensures the seamless flow of electrons through metabolic pathways. For example, in bacterial metabolism, glucose undergoes oxidation to carbon dioxide, while oxygen is simultaneously reduced to...
1.1K
01:16What is Homeostasis?
57.1K
Maintaining homeostasis requires that the body continuously maintain its internal conditions. Each physiological condition has a particular set point, from body temperature to blood pressure to levels of certain nutrients. A set point is the physiological value around which the normal range fluctuates. A normal range is a restricted set of values that is optimally healthful and stable. For example, the set point for normal human body temperature is approximately 37°C (98.6°F).
57.1K
01:31pH Homeostasis
19.5K
Acid-base homeostasis is essential for maintaining normal physiological activities in humans. The pH of various body fluids is strictly regulated because it is critical for the optimal activity of enzymes involved in metabolic reactions. Enzymes are basically proteins, so, any significant change in pH can affect their structure and activity. In humans, pH is regulated using three primary mechanisms— chemical buffer systems, respiratory regulation, and renal regulation.
Respiratory...
Respiratory...
19.5K
01:49Golgi Apparatus
104.0K
As they leave the Endoplasmic Reticulum (ER), properly folded and assembled proteins are selectively packaged into vesicles. These vesicles are transported by microtubule-based motor proteins and fuse together to form vesicular tubular clusters, subsequently arriving at the Golgi apparatus, a eukaryotic endomembrane organelle that often has a distinctive ribbon-like appearance.
104.0K