Roles of Mitochondria in Neutrophils

Overview

Journal Front Immunol

Specialty Allergy & Immunology

Date 2022 Sep 9

PMID 36081497

Authors

Ziming Cao

Meng Zhao

Hao Sun

Liang Hu

Yunfeng Chen

Zhichao Fan

Affiliations

Soon will be listed here.

Abstract

Neutrophils are the most abundant leukocyte in human blood. They are critical for fighting infections and are involved in inflammatory diseases. Mitochondria are indispensable for eukaryotic cells, as they control the biochemical processes of respiration and energy production. Mitochondria in neutrophils have been underestimated since glycolysis is a major metabolic pathway for fuel production in neutrophils. However, several studies have shown that mitochondria are greatly involved in multiple neutrophil functions as well as neutrophil-related diseases. In this review, we focus on how mitochondrial components, metabolism, and related genes regulate neutrophil functions and relevant diseases.

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References

Bao Y, Ledderose C, Seier T, Graf A, Brix B, Chong E . Mitochondria regulate neutrophil activation by generating ATP for autocrine purinergic signaling. J Biol Chem. 2014; 289(39):26794-26803. PMC: 4175322. DOI: 10.1074/jbc.M114.572495. View

Jiao H, Jiang D, Du W, Ji L, Yang Y, Li X . Mitocytosis, a migrasome-mediated mitochondrial quality-control process. Cell. 2021; 184(11):2896-2910.e13. DOI: 10.1016/j.cell.2021.04.027. View

Yang C, Wang Z, Li L, Zhang Z, Jin X, Wu P . Aged neutrophils form mitochondria-dependent vital NETs to promote breast cancer lung metastasis. J Immunother Cancer. 2021; 9(10). PMC: 8559246. DOI: 10.1136/jitc-2021-002875. View

Wallace D, Singh G, Lott M, Hodge J, Schurr T, Lezza A . Mitochondrial DNA mutation associated with Leber's hereditary optic neuropathy. Science. 1988; 242(4884):1427-30. DOI: 10.1126/science.3201231. View

Paupe V, Prudent J . New insights into the role of mitochondrial calcium homeostasis in cell migration. Biochem Biophys Res Commun. 2017; 500(1):75-86. PMC: 5930976. DOI: 10.1016/j.bbrc.2017.05.039. View

Yin T, Luo J, Huang D, Li H . Current Progress of Mitochondrial Genome Editing by CRISPR. Front Physiol. 2022; 13:883459. PMC: 9108280. DOI: 10.3389/fphys.2022.883459. View

Weiss E, Hanzelmann D, Fehlhaber B, Klos A, von Loewenich F, Liese J . Formyl-peptide receptor 2 governs leukocyte influx in local infections. FASEB J. 2017; 32(1):26-36. PMC: 5731131. DOI: 10.1096/fj.201700441R. View

Li P, Li M, Lindberg M, Kennett M, Xiong N, Wang Y . PAD4 is essential for antibacterial innate immunity mediated by neutrophil extracellular traps. J Exp Med. 2010; 207(9):1853-62. PMC: 2931169. DOI: 10.1084/jem.20100239. View

Chakravarti A, Raquil M, Tessier P, Poubelle P . Surface RANKL of Toll-like receptor 4-stimulated human neutrophils activates osteoclastic bone resorption. Blood. 2009; 114(8):1633-44. DOI: 10.1182/blood-2008-09-178301. View

10.

Rodriguez-Espinosa O, Rojas-Espinosa O, Moreno-Altamirano M, Lopez-Villegas E, Sanchez-Garcia F . Metabolic requirements for neutrophil extracellular traps formation. Immunology. 2014; 145(2):213-24. PMC: 4427386. DOI: 10.1111/imm.12437. View

11.

Contis A, Mitrovic S, Lavie J, Douchet I, Lazaro E, Truchetet M . Neutrophil-derived mitochondrial DNA promotes receptor activator of nuclear factor κB and its ligand signalling in rheumatoid arthritis. Rheumatology (Oxford). 2017; 56(7):1200-1205. DOI: 10.1093/rheumatology/kex041. View

12.

Carelli V, Carbonelli M, de Coo I, Kawasaki A, Klopstock T, Lagreze W . International Consensus Statement on the Clinical and Therapeutic Management of Leber Hereditary Optic Neuropathy. J Neuroophthalmol. 2017; 37(4):371-381. DOI: 10.1097/WNO.0000000000000570. View

13.

Mok B, de Moraes M, Zeng J, Bosch D, Kotrys A, Raguram A . A bacterial cytidine deaminase toxin enables CRISPR-free mitochondrial base editing. Nature. 2020; 583(7817):631-637. PMC: 7381381. DOI: 10.1038/s41586-020-2477-4. View

14.

Zhou W, Hsu A, Wang Y, Syahirah R, Wang T, Jeffries J . Mitofusin 2 regulates neutrophil adhesive migration and the actin cytoskeleton. J Cell Sci. 2020; 133(17). PMC: 7491649. DOI: 10.1242/jcs.248880. View

15.

Riganti C, Gazzano E, Polimeni M, Costamagna C, Bosia A, Ghigo D . Diphenyleneiodonium inhibits the cell redox metabolism and induces oxidative stress. J Biol Chem. 2004; 279(46):47726-31. DOI: 10.1074/jbc.M406314200. View

16.

Wei Y, Cui L, Peng B . Mitochondrial DNA mutations in late-onset Leigh syndrome. J Neurol. 2018; 265(10):2388-2395. DOI: 10.1007/s00415-018-9014-5. View

17.

Wang Y, Wang W, Wang N, Tall A, Tabas I . Mitochondrial Oxidative Stress Promotes Atherosclerosis and Neutrophil Extracellular Traps in Aged Mice. Arterioscler Thromb Vasc Biol. 2017; 37(8):e99-e107. PMC: 5535797. DOI: 10.1161/ATVBAHA.117.309580. View

18.

Sun H, Hu L, Fan Z . β2 integrin activation and signal transduction in leukocyte recruitment. Am J Physiol Cell Physiol. 2021; 321(2):C308-C316. PMC: 8424673. DOI: 10.1152/ajpcell.00560.2020. View

19.

Monteith A, Miller J, Maxwell C, Chazin W, Skaar E . Neutrophil extracellular traps enhance macrophage killing of bacterial pathogens. Sci Adv. 2021; 7(37):eabj2101. PMC: 8442908. DOI: 10.1126/sciadv.abj2101. View

20.

Liu W, Hsu A, Wang Y, Lin T, Sun H, Pachter J . Mitofusin-2 regulates leukocyte adhesion and β2 integrin activation. J Leukoc Biol. 2021; 111(4):771-791. PMC: 8901796. DOI: 10.1002/JLB.1A0720-471R. View