DOI QR코드

DOI QR Code

Mitochondria-mediated defense mechanisms against pathogens in Caenorhabditis elegans

  • Kwon, Sujeong (Department of Life Sciences, Pohang University of Science and Technology) ;
  • Kim, Eun Ji E. (Department of Life Sciences, Pohang University of Science and Technology) ;
  • Lee, Seung-Jae V. (Department of Life Sciences, Pohang University of Science and Technology)
  • Received : 2018.04.26
  • Published : 2018.06.30

Abstract

Mitochondria are crucial organelles that generate cellular energy and metabolites. Recent studies indicate that mitochondria also regulate immunity. In this review, we discuss key roles of mitochondria in immunity against pathogen infection and underlying mechanisms, focusing on discoveries using Caenorhabditis elegans. Various mitochondrial processes, including mitochondrial surveillance mechanisms, mitochondrial unfolded protein response ($UPR^{mt}$), mitophagy, and reactive oxygen species (ROS) production, contribute to immune responses and resistance of C. elegans against pathogens. Biological processes of C. elegans are usually conserved across phyla. Thus, understanding the mechanisms of mitochondria-mediated defense responses in C. elegans may provide insights into similar mechanisms in complex organisms, including mammals.

Keywords

References

  1. West AP, Shadel GS and Ghosh S (2011) Mitochondria in innate immune responses. Nat Rev Immunol 11, 389-402 https://doi.org/10.1038/nri2975
  2. Mehta MM, Weinberg SE and Chandel NS (2017) Mitochondrial control of immunity: beyond ATP. Nat Rev Immunol 17, 608 https://doi.org/10.1038/nri.2017.66
  3. Ewbank JJ and Pujol N (2016) Local and long-range activation of innate immunity by infection and damage in C. elegans. Curr Opin Immunol 38, 1-7 https://doi.org/10.1016/j.coi.2015.09.005
  4. Kim DH and Ewbank JJ (2015) Signaling in the innate immune response. WormBook, 1-51
  5. Prasai K (2017) Regulation of mitochondrial structure and function by protein import: A current review. Pathophysiology 24, 107-122 https://doi.org/10.1016/j.pathophys.2017.03.001
  6. Gerwien F, Skrahina V, Kasper L, Hube B and Brunke S (2018) Metals in fungal virulence. FEMS Microbiol Rev 42
  7. Chandrangsu P, Rensing C and Helmann JD (2017) Metal homeostasis and resistance in bacteria. Nat Rev Microbiol 15, 338-350 https://doi.org/10.1038/nrmicro.2017.15
  8. Shore DE and Ruvkun G (2013) A Cytoprotective Perspective on Longevity Regulation. Trends Cell Biol 23, 409-420 https://doi.org/10.1016/j.tcb.2013.04.007
  9. Liu Y, Samuel BS, Breen PC and Ruvkun G (2014) Caenorhabditis elegans pathways that surveil and defend mitochondria. Nature 508, 406-410 https://doi.org/10.1038/nature13204
  10. Tjahjono E and Kirienko NV (2017) A conserved mitochondrial surveillance pathway is required for defense against Pseudomonas aeruginosa. PLoS Genet 13, e1006876 https://doi.org/10.1371/journal.pgen.1006876
  11. Kang D, Kirienko DR, Webster P, Fisher AL and Kirienko NV (2018) Pyoverdine, a siderophore from Pseudomonas aeruginosa, translocates into C. elegans, removes iron, and activates a distinct host response. Virulence, 1-41
  12. Pickles S, Vigie P and Youle RJ (2018) Mitophagy and Quality Control Mechanisms in Mitochondrial Maintenance. Curr Biol 28, R170-R185 https://doi.org/10.1016/j.cub.2018.01.004
  13. Mouton-Liger F, Jacoupy M, Corvol J-C and Corti O (2017) PINK1/Parkin-Dependent Mitochondrial Surveillance: From Pleiotropy to Parkinson's Disease. Front Mol Neurosci 10, 120 https://doi.org/10.3389/fnmol.2017.00120
  14. Narendra DP, Jin SM, Tanaka A et al (2010) PINK1 is selectively stabilized on impaired mitochondria to activate Parkin. PLoS Biol 8, e1000298 https://doi.org/10.1371/journal.pbio.1000298
  15. Yang Y, Gehrke S, Imai Y et al (2006) Mitochondrial pathology and muscle and dopaminergic neuron degeneration caused by inactivation of Drosophila Pink1 is rescued by Parkin. Proc Natl Acad Sci U S A 103, 10793-10798 https://doi.org/10.1073/pnas.0602493103
  16. Clark IE, Dodson MW, Jiang C et al (2006) Drosophila pink1 is required for mitochondrial function and interacts genetically with parkin. Nature 441, 1162-1166 https://doi.org/10.1038/nature04779
  17. Park J, Lee SB, Lee S et al (2006) Mitochondrial dysfunction in Drosophila PINK1 mutants is complemented by parkin. Nature 441, 1157-1161 https://doi.org/10.1038/nature04788
  18. Harper JW, Ordureau A and Heo JM (2018) Building and decoding ubiquitin chains for mitophagy. Nat Rev Mol Cell Biol 19, 93-108 https://doi.org/10.1038/nrm.2017.129
  19. Kirienko NV, Ausubel FM and Ruvkun G (2015) Mitophagy confers resistance to siderophore-mediated killing by Pseudomonas aeruginosa. Proc Natl Acad Sci U S A 112, 1821 https://doi.org/10.1073/pnas.1424954112
  20. Jovaisaite V, Mouchiroud L and Auwerx J (2014) The mitochondrial unfolded protein response, a conserved stress response pathway with implications in health and disease. J Exp Biol 217, 137 https://doi.org/10.1242/jeb.090738
  21. Hetz C and Papa FR (2018) The Unfolded Protein Response and Cell Fate Control. Mol Cell 69, 169-181 https://doi.org/10.1016/j.molcel.2017.06.017
  22. Powers ET and Balch WE (2013) Diversity in the origins of proteostasis networks - a driver for protein function in evolution. Nat Rev Mol Cell Biol 14, 237 https://doi.org/10.1038/nrm3542
  23. Shpilka T and Haynes CM (2018) The mitochondrial UPR: mechanisms, physiological functions and implications in ageing. Nat Rev Mol Cell Biol 19, 109-120
  24. Frakes AE and Dillin A (2017) The $UPR^{ER}$ Sensor and Coordinator of Organismal Homeostasis. Mol Cell 66, 761-771 https://doi.org/10.1016/j.molcel.2017.05.031
  25. Sala AJ, Bott LC and Morimoto RI (2017) Shaping proteostasis at the cellular, tissue, and organismal level. J Cell Biol 216, 1231-1241 https://doi.org/10.1083/jcb.201612111
  26. Moehle EA, Shen K and Dillin A (2018) Mitochondrial Proteostasis in the Context of Cellular and Organismal Health and Aging. J Biol Chem [Epub ahead of print]
  27. Nargund AM, Pellegrino MW, Fiorese CJ, Baker BM and Haynes CM (2012) Mitochondrial import efficiency of ATFS-1 regulates mitochondrial UPR activation. Science 337, 587-590 https://doi.org/10.1126/science.1223560
  28. Haynes CM, Yang Y, Blais SP, Neubert TA and Ron D (2010) The matrix peptide exporter HAF-1 signals a mitochondrial UPR by activating the transcription factor ZC376.7 in C. elegans. Mol Cell 37, 529-540 https://doi.org/10.1016/j.molcel.2010.01.015
  29. Haynes CM, Petrova K, Benedetti C, Yang Y and Ron D (2007) ClpP mediates activation of a mitochondrial unfolded protein response in C. elegans. Dev Cell 13, 467-480 https://doi.org/10.1016/j.devcel.2007.07.016
  30. Pellegrino MW, Nargund AM, Kirienko NV, Gillis R, Fiorese CJ and Haynes CM (2014) Mitochondrial UPR-regulated innate immunity provides resistance to pathogen infection. Nature 516, 414-417 https://doi.org/10.1038/nature13818
  31. Nargund AM, Fiorese CJ, Pellegrino MW, Deng P and Haynes CM (2015) Mitochondrial and nuclear accumulation of the transcription factor ATFS-1 promotes OXPHOS recovery during the UPR(mt). Mol Cell 58, 123-133 https://doi.org/10.1016/j.molcel.2015.02.008
  32. Jeong DE, Lee D, Hwang SY et al (2017) Mitochondrial chaperone HSP-60 regulates anti-bacterial immunity via p38 MAP kinase signaling. EMBO J 36, 1046-1065 https://doi.org/10.15252/embj.201694781
  33. Cohen LB and Troemel ER (2015) Microbial pathogenesis and host defense in the nematode C. elegans. Curr Opin Microbiol 23, 94-101 https://doi.org/10.1016/j.mib.2014.11.009
  34. Van Raamsdonk JM and Hekimi S (2010) Reactive Oxygen Species and Aging in Caenorhabditis elegans: Causal or Casual Relationship? Antioxid Redox Signal 13, 1911-1953 https://doi.org/10.1089/ars.2010.3215
  35. Hwang AB and Lee SJ (2011) Regulation of life span by mitochondrial respiration: the HIF-1 and ROS connection. Aging (Albany NY) 3, 304-310
  36. Hwang AB, Ryu EA, Artan M et al (2014) Feedback regulation via AMPK and HIF-1 mediates ROS-dependent longevity in Caenorhabditis elegans. Proc Natl Acad Sci U S A 111, E4458-4467 https://doi.org/10.1073/pnas.1411199111
  37. Lee SJ, Hwang AB and Kenyon C (2010) Inhibition of respiration extends C. elegans life span via reactive oxygen species that increase HIF-1 activity. Curr Biol 20, 2131-2136 https://doi.org/10.1016/j.cub.2010.10.057
  38. Yang W and Hekimi S (2010) A Mitochondrial Superoxide Signal Triggers Increased Longevity in Caenorhabditis elegans. PLoS Biol 8, e1000556 https://doi.org/10.1371/journal.pbio.1000556
  39. Tang H and Pang S (2016) Proline Catabolism Modulates Innate Immunity in Caenorhabditis elegans. Cell Rep 17, 2837-2844 https://doi.org/10.1016/j.celrep.2016.11.038
  40. Chavez V, Mohri-Shiomi A and Garsin DA (2009) Ce-Duox1/BLI-3 generates reactive oxygen species as a protective innate immune mechanism in Caenorhabditis elegans. Infect Immun 77, 4983-4989 https://doi.org/10.1128/IAI.00627-09
  41. van der Hoeven R, McCallum KC, Cruz MR and Garsin DA (2011) Ce-Duox1/BLI-3 Generated Reactive Oxygen Species Trigger Protective SKN-1 Activity via p38 MAPK Signaling during Infection in C. elegans. PLoS Pathog 7, e1002453 https://doi.org/10.1371/journal.ppat.1002453
  42. McCallum KC and Garsin DA (2016) The Role of Reactive Oxygen Species in Modulating the Caenorhabditis elegans Immune Response. PLoS Pathog 12, e1005923 https://doi.org/10.1371/journal.ppat.1005923
  43. Xu S and Chisholm AD (2014) C. elegans epidermal wounding induces a mitochondrial ROS burst that promotes wound repair. Dev Cell 31, 48-60 https://doi.org/10.1016/j.devcel.2014.08.002
  44. Koliaki C and Roden M (2016) Alterations of Mitochondrial Function and Insulin Sensitivity in Human Obesity and Diabetes Mellitus. Annu Rev Nutr 36, 337-367 https://doi.org/10.1146/annurev-nutr-071715-050656
  45. Kauppila TES, Kauppila JHK and Larsson NG (2017) Mammalian Mitochondria and Aging: An Update. Cell Metab 25, 57-71 https://doi.org/10.1016/j.cmet.2016.09.017
  46. Lima A, Burgstaller J, Sanchez-Nieto JM and Rodriguez TA (2018) The Mitochondria and the Regulation of Cell Fitness During Early Mammalian Development. Curr Top Dev Biol 128, 339-363