Mitochondrial Control of Innate Immune Responses

Overview

Journal Front Immunol

Specialty Allergy & Immunology

Date 2023 Jun 16

PMID 37325622

Authors

Shasha Chen

Zhiyong Liao

Pinglong Xu

Affiliations

Soon will be listed here.

Abstract

Mitochondria are versatile organelles and essential components of numerous biological processes such as energy metabolism, signal transduction, and cell fate determination. In recent years, their critical roles in innate immunity have come to the forefront, highlighting impacts on pathogenic defense, tissue homeostasis, and degenerative diseases. This review offers an in-depth and comprehensive examination of the multifaceted mechanisms underlying the interactions between mitochondria and innate immune responses. We will delve into the roles of healthy mitochondria as platforms for signalosome assembly, the release of mitochondrial components as signaling messengers, and the regulation of signaling mitophagy, particularly to cyclic GMP-AMP synthase-stimulator of interferon genes (cGAS-STING) signaling and inflammasomes. Furthermore, the review will explore the impacts of mitochondrial proteins and metabolites on modulating innate immune responses, the polarization of innate immune cells, and their implications on infectious and inflammatory diseases.

Citing Articles

The Essential Role of Mitochondrial Dynamics in Viral Infections.

Duan X, Liu R, Lan W, Liu S Int J Mol Sci. 2025; 26(5).

PMID: 40076578 PMC: 11900267. DOI: 10.3390/ijms26051955.

Are Mitochondria a Potential Target for Treating β-Thalassemia?.

Pierro E, Stefano V, Migone De Amicis M, Graziadei G J Clin Med. 2025; 14(4).

PMID: 40004626 PMC: 11856739. DOI: 10.3390/jcm14041095.

Prediction of Hepatocellular Carcinoma Prognosis and Immunotherapy Response Using Mitochondrial Dysregulation Features.

Yu J, Wu S, Gong J, Deng W, Xiao Z, Wu L J Cell Mol Med. 2025; 29(3):e70389.

PMID: 39910622 PMC: 11798730. DOI: 10.1111/jcmm.70389.

Involvement of TGF-β, mTOR, and inflammatory mediators in aging alterations during myxomatous mitral valve disease in a canine model.

Grzeczka A, Graczyk S, Kordowitzki P Geroscience. 2025; .

PMID: 39865135 DOI: 10.1007/s11357-025-01520-0.

CMPK2 promotes NLRP3 inflammasome activation via mtDNA-STING pathway in house dust mite-induced allergic rhinitis.

Zheng Y, Xie Y, Li J, Cao Y, Li M, Cao Q Clin Transl Med. 2025; 15(1):e70180.

PMID: 39799434 PMC: 11726638. DOI: 10.1002/ctm2.70180.

References

Chen K, Demarco B, Heilig R, Shkarina K, Boettcher A, Farady C . Extrinsic and intrinsic apoptosis activate pannexin-1 to drive NLRP3 inflammasome assembly. EMBO J. 2019; 38(10). PMC: 6517827. DOI: 10.15252/embj.2019101638. View

Zhong Z, Umemura A, Sanchez-Lopez E, Liang S, Shalapour S, Wong J . NF-κB Restricts Inflammasome Activation via Elimination of Damaged Mitochondria. Cell. 2016; 164(5):896-910. PMC: 4769378. DOI: 10.1016/j.cell.2015.12.057. View

Riley J, Tait S . Mitochondrial DNA in inflammation and immunity. EMBO Rep. 2020; 21(4):e49799. PMC: 7132203. DOI: 10.15252/embr.201949799. View

Kozaki T, Komano J, Kanbayashi D, Takahama M, Misawa T, Satoh T . Mitochondrial damage elicits a TCDD-inducible poly(ADP-ribose) polymerase-mediated antiviral response. Proc Natl Acad Sci U S A. 2017; 114(10):2681-2686. PMC: 5347618. DOI: 10.1073/pnas.1621508114. View

Storek K, Gertsvolf N, Ohlson M, Monack D . cGAS and Ifi204 cooperate to produce type I IFNs in response to Francisella infection. J Immunol. 2015; 194(7):3236-45. PMC: 4367159. DOI: 10.4049/jimmunol.1402764. View

Keinan N, Tyomkin D, Shoshan-Barmatz V . Oligomerization of the mitochondrial protein voltage-dependent anion channel is coupled to the induction of apoptosis. Mol Cell Biol. 2010; 30(24):5698-709. PMC: 3004265. DOI: 10.1128/MCB.00165-10. View

Bonora M, Giorgi C, Pinton P . Molecular mechanisms and consequences of mitochondrial permeability transition. Nat Rev Mol Cell Biol. 2021; 23(4):266-285. DOI: 10.1038/s41580-021-00433-y. View

Schoggins J, MacDuff D, Imanaka N, Gainey M, Shrestha B, Eitson J . Corrigendum: Pan-viral specificity of IFN-induced genes reveals new roles for cGAS in innate immunity. Nature. 2015; 525(7567):144. PMC: 8323779. DOI: 10.1038/nature14555. View

Lee S, Park S, Lee S, Lee S, Son M, Choi Y . Synoviocyte apoptosis may differentiate responder and non-responder patients to methotrexate treatment in rheumatoid arthritis. Arch Pharm Res. 2014; 37(10):1286-94. DOI: 10.1007/s12272-014-0365-x. View

10.

Riley J, Quarato G, Cloix C, Lopez J, OPrey J, Pearson M . Mitochondrial inner membrane permeabilisation enables mtDNA release during apoptosis. EMBO J. 2018; 37(17). PMC: 6120664. DOI: 10.15252/embj.201899238. View

11.

Zhong Z, Liang S, Sanchez-Lopez E, He F, Shalapour S, Lin X . New mitochondrial DNA synthesis enables NLRP3 inflammasome activation. Nature. 2018; 560(7717):198-203. PMC: 6329306. DOI: 10.1038/s41586-018-0372-z. View

12.

Infantino V, Iacobazzi V, Palmieri F, Menga A . ATP-citrate lyase is essential for macrophage inflammatory response. Biochem Biophys Res Commun. 2013; 440(1):105-11. DOI: 10.1016/j.bbrc.2013.09.037. View

13.

Kim Y, Park J, Kim S, Kim M, Kang M, Kwak C . PKR Senses Nuclear and Mitochondrial Signals by Interacting with Endogenous Double-Stranded RNAs. Mol Cell. 2018; 71(6):1051-1063.e6. DOI: 10.1016/j.molcel.2018.07.029. View

14.

Wang H, Li T, Chen S, Gu Y, Ye S . Neutrophil Extracellular Trap Mitochondrial DNA and Its Autoantibody in Systemic Lupus Erythematosus and a Proof-of-Concept Trial of Metformin. Arthritis Rheumatol. 2015; 67(12):3190-200. DOI: 10.1002/art.39296. View

15.

Borowski L, Dziembowski A, Hejnowicz M, Stepien P, Szczesny R . Human mitochondrial RNA decay mediated by PNPase-hSuv3 complex takes place in distinct foci. Nucleic Acids Res. 2012; 41(2):1223-40. PMC: 3553951. DOI: 10.1093/nar/gks1130. View

16.

Phillip West A, Khoury-Hanold W, Staron M, Tal M, Pineda C, Lang S . Mitochondrial DNA stress primes the antiviral innate immune response. Nature. 2015; 520(7548):553-7. PMC: 4409480. DOI: 10.1038/nature14156. View

17.

Bai D, Du J, Bu X, Cao W, Sun T, Zhao J . ALDOA maintains NLRP3 inflammasome activation by controlling AMPK activation. Autophagy. 2021; 18(7):1673-1693. PMC: 9298449. DOI: 10.1080/15548627.2021.1997051. View

18.

Wang Y, Li N, Zhang X, Horng T . Mitochondrial metabolism regulates macrophage biology. J Biol Chem. 2021; 297(1):100904. PMC: 8294576. DOI: 10.1016/j.jbc.2021.100904. View

19.

Nassour J, Aguiar L, Correia A, Schmidt T, Mainz L, Przetocka S . Telomere-to-mitochondria signalling by ZBP1 mediates replicative crisis. Nature. 2023; 614(7949):767-773. PMC: 9946831. DOI: 10.1038/s41586-023-05710-8. View

20.

Chandel N . Mitochondria. Cold Spring Harb Perspect Biol. 2021; 13(3). PMC: 7919390. DOI: 10.1101/cshperspect.a040543. View