Publication
Opposing action of NCoR1 and PGC-1 alpha in mitochondrial redox homeostasis
Abstract
The ability to respond to fluctuations of reactive oxygen species (ROS) within the cell is a central aspect of mammalian physiology. This dynamic process depends on the coordinated action of transcriptional factors to promote the expression of genes encoding for antioxidant enzymes. Here, we demonstrate that the transcriptional coregulators, PGC-1 alpha and NCoR1, are essential mediators of mitochondrial redox homeostasis in skeletal muscle cells. Our findings reveal an antagonistic role of these coregulators in modulating mitochondrial antioxidant induction through Sod2 transcriptional control. Importantly, the activation of this mechanism by either PGC-1 alpha overexpression or NCoR1 knockdown attenuates mitochondrial ROS levels and prevents cell death caused by lipid overload in skeletal muscle cells. The opposing actions of coactivators and corepressors, therefore, exert a commanding role over cellular antioxidant capacity.
Official source
About this result
This page is automatically generated and may contain information that is not correct, complete, up-to-date, or relevant to your search query. The same applies to every other page on this website. Please make sure to verify the information with EPFL's official sources.
Ontological neighbourhood
Related concepts (33)
Reactive oxygen species
In chemistry, reactive oxygen species (ROS) are highly reactive chemicals formed from diatomic oxygen (). Examples of ROS include peroxides, superoxide, hydroxyl radical, singlet oxygen, and alpha-oxygen. The reduction of molecular oxygen () produces superoxide (), which is the precursor to most other reactive oxygen species: O2{} + e^- -> \ ^\bullet O2- Dismutation of superoxide produces hydrogen peroxide (): 2 H+{} + 2 \ ^\bullet O2^-{} -> H2O2{} + O2 Hydrogen peroxide in turn may be partially reduced, thus forming hydroxide ions and hydroxyl radicals (), or fully reduced to water: H2O2{} + e^- -> HO^-{} + \ ^\bullet OH 2 H+ + 2 e- + H2O2 -> 2 H2O In a biological context, ROS are byproducts of the normal metabolism of oxygen.
Antioxidant
Antioxidants are compounds that inhibit oxidation (usually occurring as autoxidation), a chemical reaction that can produce free radicals. Autoxidation leads to degradation of organic compounds, including living matter. Antioxidants are frequently added to industrial products, such as polymers, fuels, and lubricants, to extend their usable lifetimes. Food are also treated with antioxidants to forestall spoilage, in particular the rancidification of oils and fats.
Transcription factor
In molecular biology, a transcription factor (TF) (or sequence-specific DNA-binding factor) is a protein that controls the rate of transcription of genetic information from DNA to messenger RNA, by binding to a specific DNA sequence. The function of TFs is to regulate—turn on and off—genes in order to make sure that they are expressed in the desired cells at the right time and in the right amount throughout the life of the cell and the organism.
Related publications (40)
Products and methods for promoting myogenesis
Johan Auwerx, Martin Rainer Wohlwend
The present invention relates generally to the field of long non-coding RNAs and transcription factors and modulation of their expression for use in medicine and agriculture, such as the treatment and prevention of diseases associated with muscle atrophy a ...
2022Enhancing mitochondrial quality control to fight neuromuscular degeneration in aging and disease
Loss of mitochondrial function and proteostasis typify aging and age-associated degenerative disorders such as Alzheimer's disease and muscle aging. To date, no cure or preventive measure is available to manage these conditions. Alterations of cellular pro ...
EPFL2021CO-REGULATION OF ENDOTHELIAL AND MYOGENIC CELL FATES THROUGH INTERCELLULAR CROSSTALK IN SKELETAL MUSCLE
Skeletal muscle is one of the most dynamic organs in the human body, which has a vigorous potential to regenerate and adapt to environmental changes. Depending on environments, skeletal muscle enables essential life activities to survive by controlling mov ...
EPFL2021Related MOOCs (16)
Neuroscience Reconstructed: Cell Biology
This course will provide the fundamental knowledge in neuroscience required to
understand how the brain is organised and how function at multiple scales is
integrated to give rise to cognition and beh
Neuroscience Reconstructed: Cell Biology
This course will provide the fundamental knowledge in neuroscience required to
understand how the brain is organised and how function at multiple scales is
integrated to give rise to cognition and beh
Neuroscience Reconstructed: Genetics and Brain Development
This course will provide the fundamental knowledge in neuroscience required to
understand how the brain is organised and how function at multiple scales is
integrated to give rise to cognition and beh