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Mitochondrial DNA in NLRP3 inflammasome activation

Yanbing Qiu1, Yumei Huang1, Meilin Chen1

  • 1Department of Laboratory Medicine, Central South University, Changsha, Hunan, People's Republic of China; Department of Laboratory Medicine, The Third Xiangya Hospital, Central South University, Changsha, Hunan, People's Republic of China.

International Immunopharmacology
|March 29, 2022
PubMed

Insights

Mitochondrial DNA (mtDNA) activates the NLRP3 inflammasome through distinct mechanisms. Intracellular mtDNA directly binds NLRP3, while extracellular mtDNA acts as a damage-associated molecular pattern (DAMP) in NLRP3 inflammasome activation.

Area of Science:

  • Immunology
  • Cell Biology
  • Molecular Biology

Background:

  • The NLRP3 inflammasome is a crucial immune complex activated by various stimuli, leading to inflammatory responses.
  • NLRP3 inflammasome activation involves caspase-1, pro-inflammatory cytokines IL-1β and IL-18, and pyroptosis via GSDMD.
  • Tight regulation of inflammasome signaling is essential due to its role in numerous diseases.

Purpose of the Study:

  • To elucidate the distinct roles of intracellular and extracellular mitochondrial DNA (mtDNA) in NLRP3 inflammasome activation.
  • To explore how mtDNA-mediated NLRP3 inflammasome activation interacts with other known activation pathways.

Main Methods:

  • Review and synthesis of existing literature on NLRP3 inflammasome activation and mitochondrial DNA.
  • Analysis of the molecular mechanisms by which mtDNA triggers inflammasome signaling.

Main Results:

  • Intracellular mtDNA, prone to oxidation, directly binds and activates NLRP3 in the cytoplasm.
  • Extracellular mtDNA functions as a damage-associated molecular pattern (DAMP), contributing to NLRP3 inflammasome priming and activation.
  • Distinct pathways exist for mtDNA-mediated inflammasome activation.

Conclusions:

  • Mitochondrial DNA is a significant endogenous activator of the NLRP3 inflammasome.
  • Understanding these mtDNA-NLRP3 interactions is vital for comprehending disease pathogenesis and developing therapeutic strategies.
Keywords:
ActivationMitochondrial DNANLRP3 inflammasome

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