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Updated: May 27, 2026
04:32
Extraction of Cofactor F420 for Analysis of Polyglutamate Tail Length from Methanogenic Pure Cultures and Environmental Samples
Published on: October 14, 2021
Fumarate loss destabilizes mitochondria and activates cGAS-STING in OLP
Yanxing Hu1, Huyan Chen2, Chenyun Ding1
1Department of Stomatology, Huashan Hospital, Fudan University, Shanghai 200040, China.
Summary
Oral lichen planus (OLP) involves a metabolic link where fumarate hydratase (FH) depletion disrupts mitochondrial function, activating innate immune pathways. Restoring fumarate levels or blocking mitochondrial DNA release can reduce inflammation.
Area of Science:
- Mitochondrial metabolism
- Innate immunity
- Chronic inflammatory diseases
Background:
- Mitochondrial metabolism and innate immune signaling are interconnected in chronic inflammatory conditions.
- Oral lichen planus (OLP) is a chronic inflammatory disease affecting mucosal tissues.
Purpose of the Study:
- To investigate the link between the TCA cycle and mucosal inflammation in OLP.
- To identify the role of fumarate hydratase (FH) in OLP pathogenesis.
- To explore fumarate as a potential therapeutic target.
Main Methods:
- Multi-omics analysis of OLP tissues and cells.
- Investigating the effects of FH modulation and fumarate supplementation.
- Utilizing mtDNA depletion models and assessing immune pathway activation (cGAS-STING).
Main Results:
- FH upregulation in OLP leads to fumarate depletion and mitochondrial dysfunction.
- Fumarate depletion promotes mtDNA release and activates the cGAS-STING innate immune pathway.
- FH inhibition or fumarate supplementation (MMF) ameliorates inflammation by restoring mitochondrial homeostasis and reducing mtDNA leakage.
Conclusions:
- A functional FH-fumarate-mtDNA-cGAS-STING axis drives inflammation in OLP.
- Fumarate acts as a key metabolic regulator of mitochondrial immune surveillance.
- Targeting fumarate metabolism offers a potential therapeutic strategy for non-infectious mucosal inflammation.
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