The Role of Mitophagy in Innate Immune Responses Triggered by Mitochondrial Stress

Overview

Journal Cell Commun Signal

Publisher Biomed Central

Specialties Biochemistry
Cell Biology

Date 2020 Nov 26

PMID 33239048

Citations 35

Authors

Yinjuan Song

Yang Zhou

Xiangmei Zhou

Affiliations

Soon will be listed here.

Abstract

Mitochondria are important cellular organelles involved in many different functions, from energy generation and fatty acid oxidation to cell death regulation and immune responses. Accumulating evidence indicates that mitochondrial stress acts as a key trigger of innate immune responses. Critically, the dysfunctional mitochondria can be selectively eliminated by mitophagy. The elimination of dysfunctional mitochondria may function as an effective way employed by mitophagy to keep the immune system in check. In addition, mitophagy can be utilized by pathogens for immune evasion. In this review, we summarize how mitochondrial stress triggers innate immune responses and the roles of mitophagy in innate immunity and in infection, as well as the molecular mechanisms of mitophagy. Video Abstract.

Citing Articles

Deubiquitination enzyme USP35 negatively regulates MAVS signaling to inhibit anti-tumor immunity.

Zhang H, Zhu J, He R, Xu L, Chen Y, Yu H Cell Death Dis. 2025; 16(1):138.

PMID: 40016186 PMC: 11868397. DOI: 10.1038/s41419-025-07411-8.

Bayesian-optimized deep learning for identifying essential genes of mitophagy and fostering therapies to combat drug resistance in human cancers.

Jin W, Chen J, Li Z, Yubiao Z, Peng H J Cell Mol Med. 2025; 29(2):e18254.

PMID: 39834330 PMC: 11747347. DOI: 10.1111/jcmm.18254.

Cancer cell-selective induction of mitochondrial stress and immunogenic cell death by PT-112 in human prostate cell lines.

Soler-Agesta R, Moreno-Loshuertos R, Yim C, Congenie M, Ames T, Johnson H J Transl Med. 2024; 22(1):927.

PMID: 39394618 PMC: 11470694. DOI: 10.1186/s12967-024-05739-x.

Integrative bioinformatics analysis for identifying the mitochondrial-related gene signature associated with immune infiltration in premature ovarian insufficiency.

Lu M, Li W, Zhou J, Shang J, Lin L, Liu Y BMC Med. 2024; 22(1):444.

PMID: 39379953 PMC: 11462806. DOI: 10.1186/s12916-024-03675-7.

Predicting Chemical Immunotoxicity through Data-Driven QSAR Modeling of Aryl Hydrocarbon Receptor Agonism and Related Toxicity Mechanisms.

Daood N, Russo D, Chung E, Qin X, Zhu H Environ Health (Wash). 2024; 2(7):474-485.

PMID: 39049897 PMC: 11264268. DOI: 10.1021/envhealth.4c00026.

References

Phillip West A, Shadel G, Ghosh S . Mitochondria in innate immune responses. Nat Rev Immunol. 2011; 11(6):389-402. PMC: 4281487. DOI: 10.1038/nri2975. View

Fukata M, Vamadevan A, Abreu M . Toll-like receptors (TLRs) and Nod-like receptors (NLRs) in inflammatory disorders. Semin Immunol. 2009; 21(4):242-53. DOI: 10.1016/j.smim.2009.06.005. View

Marakalala M, Ndlovu H . Signaling C-type lectin receptors in antimycobacterial immunity. PLoS Pathog. 2017; 13(6):e1006333. PMC: 5481012. DOI: 10.1371/journal.ppat.1006333. View

Galluzzi L, Kepp O, Kroemer G . Mitochondria: master regulators of danger signalling. Nat Rev Mol Cell Biol. 2012; 13(12):780-8. DOI: 10.1038/nrm3479. View

Lane N, Martin W . The energetics of genome complexity. Nature. 2010; 467(7318):929-34. DOI: 10.1038/nature09486. View

McInerney J, Pisani D, OConnell M . The ring of life hypothesis for eukaryote origins is supported by multiple kinds of data. Philos Trans R Soc Lond B Biol Sci. 2015; 370(1678):20140323. PMC: 4571563. DOI: 10.1098/rstb.2014.0323. View

Shadel G, Clayton D . Mitochondrial DNA maintenance in vertebrates. Annu Rev Biochem. 1997; 66:409-35. DOI: 10.1146/annurev.biochem.66.1.409. View

Shadel G, Horvath T . Mitochondrial ROS signaling in organismal homeostasis. Cell. 2015; 163(3):560-9. PMC: 4634671. DOI: 10.1016/j.cell.2015.10.001. View

Weinberg S, Sena L, Chandel N . Mitochondria in the regulation of innate and adaptive immunity. Immunity. 2015; 42(3):406-17. PMC: 4365295. DOI: 10.1016/j.immuni.2015.02.002. View

10.

Phillip West A . Mitochondrial dysfunction as a trigger of innate immune responses and inflammation. Toxicology. 2017; 391:54-63. DOI: 10.1016/j.tox.2017.07.016. View

11.

Lazarou M . Keeping the immune system in check: a role for mitophagy. Immunol Cell Biol. 2014; 93(1):3-10. DOI: 10.1038/icb.2014.75. View

12.

Youle R, van der Bliek A . Mitochondrial fission, fusion, and stress. Science. 2012; 337(6098):1062-5. PMC: 4762028. DOI: 10.1126/science.1219855. View

13.

DE DUVE C, WATTIAUX R . Functions of lysosomes. Annu Rev Physiol. 1966; 28:435-92. DOI: 10.1146/annurev.ph.28.030166.002251. View

14.

Youle R, Narendra D . Mechanisms of mitophagy. Nat Rev Mol Cell Biol. 2010; 12(1):9-14. PMC: 4780047. DOI: 10.1038/nrm3028. View

15.

Xu Y, Shen J, Ran Z . Emerging views of mitophagy in immunity and autoimmune diseases. Autophagy. 2019; 16(1):3-17. PMC: 6984455. DOI: 10.1080/15548627.2019.1603547. View

16.

Wiens K, Ernst J . The Mechanism for Type I Interferon Induction by Mycobacterium tuberculosis is Bacterial Strain-Dependent. PLoS Pathog. 2016; 12(8):e1005809. PMC: 4976988. DOI: 10.1371/journal.ppat.1005809. View

17.

Andreux P, Houtkooper R, Auwerx J . Pharmacological approaches to restore mitochondrial function. Nat Rev Drug Discov. 2013; 12(6):465-83. PMC: 3896945. DOI: 10.1038/nrd4023. View

18.

Barbour J, Turner N . Mitochondrial stress signaling promotes cellular adaptations. Int J Cell Biol. 2014; 2014:156020. PMC: 3920668. DOI: 10.1155/2014/156020. View

19.

Baker M, Tatsuta T, Langer T . Quality control of mitochondrial proteostasis. Cold Spring Harb Perspect Biol. 2011; 3(7). PMC: 3119916. DOI: 10.1101/cshperspect.a007559. View

20.

Kim H, Grant A, Simic M, Kohnz R, Nomura D, Durieux J . Lipid Biosynthesis Coordinates a Mitochondrial-to-Cytosolic Stress Response. Cell. 2016; 166(6):1539-1552.e16. PMC: 5922983. DOI: 10.1016/j.cell.2016.08.027. View