Related Experiment Video

Updated: Sep 2, 2025

Genotyping Single Nucleotide Polymorphisms in the Mitochondrial Genome by Pyrosequencing
07:24

Genotyping Single Nucleotide Polymorphisms in the Mitochondrial Genome by Pyrosequencing

Published on: February 10, 2023

1.6K

Come on mtDNA, light my fire

Grace M E P Lawrence1, Caroline L Holley1, Kate Schroder1

  • 1Institute for Molecular Bioscience and IMB Centre for Inflammation and Disease Research, The University of Queensland, St Lucia, QLD, Australia.

Immunity
|August 10, 2022
PubMed

Insights

Oxidized mitochondrial DNA (ox-mtDNA) triggers inflammation by activating the NLRP3 inflammasome. A new study shows FEN1 endonuclease cleaves ox-mtDNA, allowing it to escape mitochondria and activate NLRP3 and cGAS-STING pathways.

Area of Science:

  • Immunology
  • Molecular Biology
  • Cellular Biology

Background:

  • Oxidized mitochondrial DNA (ox-mtDNA) is implicated in activating NLRP3 inflammasome signaling.
  • The precise mechanism by which ox-mtDNA initiates this inflammatory response remains unclear.

Purpose of the Study:

  • To elucidate the mechanism by which oxidized mitochondrial DNA activates NLRP3 inflammasome signaling.
  • To identify the molecular players involved in ox-mtDNA processing and subsequent immune activation.

Main Methods:

  • Utilized molecular biology techniques to investigate the interaction between FEN1 endonuclease and ox-mtDNA.
  • Employed cell-based assays to monitor inflammasome activation and cytokine release.
  • Investigated the subcellular localization of ox-mtDNA fragments using microscopy.

Main Results:

  • FEN1 endonuclease was identified as a key enzyme that cleaves oxidized mitochondrial DNA.
  • Cleavage by FEN1 generates ox-mtDNA fragments that are released from mitochondria.
  • These released ox-mtDNA fragments were found to activate both NLRP3 inflammasome and cGAS-STING signaling pathways, leading to inflammation.

Conclusions:

  • FEN1-mediated cleavage of ox-mtDNA is a critical step in initiating NLRP3 inflammasome and cGAS-STING dependent inflammation.
  • This mechanism highlights a novel pathway linking mitochondrial dysfunction to innate immune activation.

More Related Videos

Author Spotlight: High-Throughput Image-Based Quantification of Mitochondrial DNA Synthesis and Distribution10:47

Author Spotlight: High-Throughput Image-Based Quantification of Mitochondrial DNA Synthesis and Distribution

Published on: May 5, 2023

3.7K
Methodology for Accurate Detection of Mitochondrial DNA Methylation12:11

Methodology for Accurate Detection of Mitochondrial DNA Methylation

Published on: May 20, 2018

13.5K

Related Concept Videos

Animal Mitochondrial Genetics02:59

Animal Mitochondrial Genetics

Among all the organelles in an animal cell, only mitochondria have their own independent genomes. Animal mitochondrial DNA is a double-stranded, closed-circular molecule with around 20,000 base pairs. Mitochondrial DNA is unique in that one of its two strands, the heavy, or H, -strand is guanine rich, whereas the complementary strand is cytosine rich and called the light, or L, -strand. Compared to nuclear DNA, mitochondrial DNA has a very low percentage of non-coding regions and is marked by...
7.9K
Non-nuclear Inheritance01:29

Non-nuclear Inheritance

Most DNA resides in the nucleus of a cell. However, some organelles in the cell cytoplasm⁠—such as chloroplasts and mitochondria⁠—also have their own DNA. These organelles replicate their DNA independently of the nuclear DNA of the cell in which they reside. Non-nuclear inheritance describes the inheritance of genes from structures other than the nucleus.
21.7K
Modern Molecular Taxonomy01:29

Modern Molecular Taxonomy

Advancements in molecular biology have revolutionized the identification and characterization of bacteria, with multiple methods leveraging DNA sequencing for enhanced precision. As sequencing technologies improve and costs decline, these approaches are increasingly used in clinical, environmental, and evolutionary studies.Multilocus Sequence Typing (MLST) examines several housekeeping genes, essential chromosomal genes encoding cellular functions, to distinguish strains. Approximately...
114
Export of Mitochondrial and Chloroplast Genes02:19

Export of Mitochondrial and Chloroplast Genes

A eukaryotic cell can have up to three different types of genetic systems: nuclear, mitochondrial, and chloroplast. During evolution, organelles have exported many genes to the nucleus; this transfer is still ongoing in some plant species. Approximately 18% of the Arabidopsis thaliana nuclear genome is thought to be derived from the chloroplast’s cyanobacterial ancestor, and around 75% of the yeast genome derived from the mitochondria’s bacterial ancestor. This export has occurred...
3.7K
Genomic DNA in Eukaryotes00:58

Genomic DNA in Eukaryotes

Eukaryotes have large genomes compared to prokaryotes. To fit their genomes into a cell, eukaryotic DNA is packaged extraordinarily tightly inside the nucleus. To achieve this, DNA is tightly wound around proteins called histones, which are packaged into nucleosomes that are joined by linker DNA and coil into chromatin fibers. Additional fibrous proteins further compact the chromatin, which is recognizable as chromosomes during certain phases of cell division.
47.6K
Pedigree Analysis01:35

Pedigree Analysis

Overview
84.8K