Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Comment
. 2019 Jun 3;38(11):e102325.
doi: 10.15252/embj.2019102325. Epub 2019 May 17.

Mitochondria and pathogen immunity: from killer to firestarter

Joel S Riley  1   2 , Stephen Wg Tait  1   2
Affiliations
Comment

Mitochondria and pathogen immunity: from killer to firestarter

Joel S Riley et al. EMBO J. .

Abstract

Serving as an innate defence mechanism, invading pathogens elicit a broad inflammatory response in cells. In this issue, Brokatzky et al (2019) report that pathogens can cause activation of BAX/BAK which permeabilises a limited number of mitochondria. Induction of DNA damage, or release of mtDNA, triggers STING-dependent pro-inflammatory cytokine expression and secretion, revealing an unexpected role for the mitochondrial apoptotic machinery in immune defence.

PubMed Disclaimer

Figures

Figure 1
Figure 1. Limited mitochondrial permeabilisation drives inflammation in response to pathogen invasion
Invading pathogens (e.g. protozoa, bacteria and viruses) trigger mitochondrial outer membrane permeabilisation (MOMP) and cytochrome c release in a limited number of mitochondria—minority MOMP. Infection with protozoa or bacteria triggers low levels of caspase activation, sufficient to activate CAD and induce DNA damage. Damaged DNA is able to activate STING to initiate inflammation. Alternatively, infection with viruses causes mtDNA release from permeabilised mitochondria, which is detected by cGAS initiating a STING‐dependent pro‐inflammatory response.
See this image and copyright information in PMC

Comment on

References

    1. Brokatzky D, Dörflinger B, Haimovici A, Weber A, Kirschnek S, Vier J, Metz A, Henschel J, Steinfeldt T, Gentle IE et al (2019) A non‐death function of the mitochondrial apoptosis apparatus in immunity. EMBO J 38: e100907 - PMC - PubMed
    1. Campbell KJ, Tait SWG (2018) Targeting BCL‐2 regulated apoptosis in cancer. Open Biol 8: 180002 - PMC - PubMed
    1. Dunphy G, Flannery SM, Almine JF, Connolly DJ, Paulus C, Jønsson KL, Jakobsen MR, Nevels MM, Bowie AG, Unterholzner L (2018) Non‐canonical activation of the DNA sensing adaptor STING by ATM and IFI16 mediates NF‐κB signaling after nuclear DNA damage. Mol Cell 71: 745–760 e5 - PMC - PubMed
    1. Giampazolias E, Zunino B, Dhayade S, Bock F, Cloix C, Cao K, Roca A, Lopez J, Ichim G, Proïcs E et al (2017) Mitochondrial permeabilization engages NF‐κB‐dependent anti‐tumour activity under caspase deficiency. Nat Cell Biol 19: 1116–1129 - PMC - PubMed
    1. Ichim G, Lopez J, Ahmed SU, Muthalagu N, Giampazolias E, Delgado ME, Haller M, Riley JS, Mason SM, Athineos D et al (2015) Limited mitochondrial permeabilization causes DNA damage and genomic instability in the absence of cell death. Mol Cell 57: 860–872 - PMC - PubMed

Substances