Identification of Mitophagy-Related Genes in Sepsis


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Abstract

Background:Numerous studies have shown that mitochondrial damage induces inflammation and activates inflammatory cells, leading to sepsis, while sepsis, a systemic inflammatory response syndrome, also exacerbates mitochondrial damage and hyperactivation. Mitochondrial autophagy eliminates aged, abnormal or damaged mitochondria to reduce intracellular mitochondrial stress and the release of mitochondria-associated molecules, thereby reducing the inflammatory response and cellular damage caused by sepsis. In addition, mitochondrial autophagy may also influence the onset and progression of sepsis, but the exact mechanisms are unclear.

Methods:In this study, we mined the available publicly available microarray data in the GEO database (Home - GEO - NCBI (nih.gov)) with the aim of identifying key genes associated with mitochondrial autophagy in sepsis.

Results:We identified four mitophagy-related genes in sepsis, TOMM20, TOMM22, TOMM40, and MFN1.

Conclusion:This study provides preliminary evidence for the treatment of sepsis and may provide a solid foundation for subsequent biological studies.

About the authors

Xiao-Yan Zeng

Department of Anesthesiology, Hospital (T.C.M) Affiliated to Southwest Medical University

Email: info@benthamscience.net

Min Zhang

Department of Anesthesiology, Hospital (T.C.M) Affiliated to Southwest Medical University

Email: info@benthamscience.net

Si-Jing Liao

Department of Anesthesiology, Hospital (T.C.M) Affiliated to Southwest Medical University

Email: info@benthamscience.net

Yong Wang

Department of Anesthesiology, Hospital (T.C.M) Affiliated to Southwest Medical University

Email: info@benthamscience.net

Ying-Bo Ren

Department of Anesthesiology, Hospital (T.C.M) Affiliated to Southwest Medical University,

Email: info@benthamscience.net

Run Li

Department of Anesthesiology, Hospital (T.C.M) Affiliated to Southwest Medical University,

Email: info@benthamscience.net

Tian-Mei Li

Department of Anesthesiology, Hospital (T.C.M) Affiliated to Southwest Medical University

Email: info@benthamscience.net

An-Qiong Mao

Department of Anesthesiology, Hospital (T.C.M) Affiliated to Southwest Medical University

Author for correspondence.
Email: info@benthamscience.net

Guang-Zhen Li

Department of Anesthesiology, Hospital (T.C.M) Affiliated to Southwest Medical University,

Author for correspondence.
Email: info@benthamscience.net

Ying Zhang

Department of Anesthesiology, Hospital (T.C.M) Affiliated to Southwest Medical University

Author for correspondence.
Email: info@benthamscience.net

References

  1. Evans L, Rhodes A, Alhazzani W, et al. Surviving sepsis campaign: International guidelines for management of sepsis and septic shock 2021. Intensive Care Med 2021; 47(11): 1181-247. doi: 10.1007/s00134-021-06506-y PMID: 34599691
  2. Heming N, Lamothe L, Ambrosi X, Annane D. Emerging drugs for the treatment of sepsis. Expert Opin Emerg Drugs 2016; 21(1): 27-37. doi: 10.1517/14728214.2016.1132700 PMID: 26751198
  3. Rello J, Valenzuela-Sánchez F, Ruiz-Rodriguez M, Moyano S. Sepsis: A review of advances in management. Adv Ther 2017; 34(11): 2393-411. doi: 10.1007/s12325-017-0622-8 PMID: 29022217
  4. Kellum JA, Formeck CL, Kernan KF, Gómez H, Carcillo JA. Subtypes and mimics of sepsis. Crit Care Clin 2022; 38(2): 195-211. doi: 10.1016/j.ccc.2021.11.013 PMID: 35369943
  5. Evans T. Diagnosis and management of sepsis. Clin Med 2018; 18(2): 146-9. doi: 10.7861/clinmedicine.18-2-146 PMID: 29626019
  6. Fleischmann-Struzek C, Mellhammar L, Rose N, et al. Incidence and mortality of hospital- and ICU-treated sepsis: results from an updated and expanded systematic review and meta-analysis. Intensive Care Med 2020; 46(8): 1552-62. doi: 10.1007/s00134-020-06151-x PMID: 32572531
  7. Bravo-San Pedro JM, Kroemer G, Galluzzi L. Autophagy and mitophagy in cardiovascular disease. Circ Res 2017; 120(11): 1812-24. doi: 10.1161/CIRCRESAHA.117.311082 PMID: 28546358
  8. Kerr JS, Adriaanse BA, Greig NH, et al. Mitophagy and Alzheimer’s Disease: Cellular and molecular mechanisms. Trends Neurosci 2017; 40(3): 151-66. doi: 10.1016/j.tins.2017.01.002 PMID: 28190529
  9. Kuma A, Komatsu M, Mizushima N. Autophagy-monitoring and autophagy-deficient mice. Autophagy 2017; 13(10): 1619-28. doi: 10.1080/15548627.2017.1343770 PMID: 28820286
  10. Senft D, Ronai ZA. UPR, autophagy, and mitochondria crosstalk underlies the ER stress response. Trends Biochem Sci 2015; 40(3): 141-8. doi: 10.1016/j.tibs.2015.01.002 PMID: 25656104
  11. Onishi M, Yamano K, Sato M, Matsuda N, Okamoto K. Molecular mechanisms and physiological functions of mitophagy. EMBO J 2021; 40(3): e104705. doi: 10.15252/embj.2020104705 PMID: 33438778
  12. Pickles S, Vigié P, Youle RJ. Mitophagy and quality control mechanisms in mitochondrial maintenance. Curr Biol 2018; 28(4): R170-85. doi: 10.1016/j.cub.2018.01.004 PMID: 29462587
  13. Zhang T, Liu Q, Gao W, Sehgal SA, Wu H. The multifaceted regulation of mitophagy by endogenous metabolites. Autophagy 2022; 18(6): 1216-39. doi: 10.1080/15548627.2021.1975914 PMID: 34583624
  14. Mohsin M, Tabassum G, Ahmad S, Ali S, Ali Syed M. The role of mitophagy in pulmonary sepsis. Mitochondrion 2021; 59: 63-75. doi: 10.1016/j.mito.2021.04.009 PMID: 33894359
  15. Chen H, Lin H, Dong B, Wang Y, Yu Y, Xie K. Hydrogen alleviates cell damage and acute lung injury in sepsis via PINK1/Parkin-mediated mitophagy. Inflamm Res 2021; 70(8): 915-30. doi: 10.1007/s00011-021-01481-y PMID: 34244821
  16. Kim MJ, Bae SH, Ryu JC, et al. SESN2/sestrin2 suppresses sepsis by inducing mitophagy and inhibiting NLRP3 activation in macrophages. Autophagy 2016; 12(8): 1272-91. doi: 10.1080/15548627.2016.1183081 PMID: 27337507
  17. Biasizzo M, Kopitar-Jerala N. Interplay between NLRP3 inflammasome and autophagy. Front Immunol 2020; 11: 591803. doi: 10.3389/fimmu.2020.591803 PMID: 33163006
  18. Zhu C, Yao R, Li L, et al. Mechanism of mitophagy and its role in sepsis induced organ dysfunction: A review. Front Cell Dev Biol 2021; 9: 664896. doi: 10.3389/fcell.2021.664896 PMID: 34164394
  19. Kimura T, Isaka Y, Yoshimori T. Autophagy and kidney inflammation. Autophagy 2017; 13(6): 997-1003. doi: 10.1080/15548627.2017.1309485 PMID: 28441075
  20. Yang H, Zhang Z. Sepsis-induced myocardial dysfunction: The role of mitochondrial dysfunction. Inflamm Res 2021; 70(4): 379-87. doi: 10.1007/s00011-021-01447-0 PMID: 33683374
  21. Barrett T, Wilhite SE, Ledoux P, et al. NCBI GEO: Archive for functional genomics data sets--update. Nucleic Acids Res 2013; 41(Database issue): D991-5. PMID: 23193258
  22. Kolde R, Laur S, Adler P, Vilo J. Robust rank aggregation for gene list integration and meta-analysis. Bioinformatics 2012; 28(4): 573-80. doi: 10.1093/bioinformatics/btr709 PMID: 22247279
  23. Szklarczyk D, Gable AL, Nastou KC, et al. The STRING database in 2021: Customizable protein–protein networks, and functional characterization of user-uploaded gene/measurement sets. Nucleic Acids Res 2021; 49(D1): D605-12. doi: 10.1093/nar/gkaa1074 PMID: 33237311
  24. Liu AC, Patel K, Vunikili RD, et al. Sepsis in the era of data-driven medicine: Personalizing risks, diagnoses, treatments and prognoses. Brief Bioinform 2020; 21(4): 1182-95. doi: 10.1093/bib/bbz059 PMID: 31190075
  25. O’Brien JM Jr, Ali NA, Aberegg SK, Abraham E. Sepsis. Am J Med 2007; 120(12): 1012-22. doi: 10.1016/j.amjmed.2007.01.035 PMID: 18060918
  26. Gullo A, Iscra F, Di Capua G, et al. Sepsis and organ dysfunction: An ongoing challenge. Minerva Anestesiol 2005; 71(11): 671-99. J. PMID: 16278628
  27. Chen P, Stanojcic M, Jeschke MG. Differences between murine and human sepsis. Surg Clin North Am 2014; 94(6): 1135-49. doi: 10.1016/j.suc.2014.08.001 PMID: 25440115
  28. Sessler CN, Shepherd W. New concepts in sepsis. Curr Opin Crit Care 2002; 8(5): 465-72. doi: 10.1097/00075198-200210000-00016 PMID: 12357117
  29. Ingels C, Gunst J, Van den Berghe G. Endocrine and metabolic alterations in sepsis and implications for treatment. Crit Care Clin 2018; 34(1): 81-96. doi: 10.1016/j.ccc.2017.08.006 PMID: 29149943
  30. Patoli D, Mignotte F, Deckert V, et al. Inhibition of mitophagy drives macrophage activation and antibacterial defense during sepsis. J Clin Invest 2020; 130(11): 5858-74. doi: 10.1172/JCI130996 PMID: 32759503
  31. Liu Q, Wu J, Zhang X, et al. Circulating mitochondrial DNA-triggered autophagy dysfunction via STING underlies sepsis-related acute lung injury. Cell Death Dis 2021; 12(7): 673. doi: 10.1038/s41419-021-03961-9 PMID: 34218252
  32. Sun Y, Cai Y, Zang QS. Cardiac autophagy in sepsis. Cells 2019; 8(2): 141. doi: 10.3390/cells8020141 PMID: 30744190
  33. Sun J, Zhang J, Tian J, et al. Mitochondria in sepsis-induced AKI. J Am Soc Nephrol 2019; 30(7): 1151-61. doi: 10.1681/ASN.2018111126 PMID: 31076465
  34. Wang Y, Zhu J, Liu Z, et al. The PINK1/PARK2/optineurin pathway of mitophagy is activated for protection in septic acute kidney injury. Redox Biol 2021; 38: 101767. doi: 10.1016/j.redox.2020.101767 PMID: 33137712
  35. Wang Y, Jasper H, Toan S, Muid D, Chang X, Zhou H. Mitophagy coordinates the mitochondrial unfolded protein response to attenuate inflammation-mediated myocardial injury. Redox Biol 2021; 45: 102049. doi: 10.1016/j.redox.2021.102049 PMID: 34174558
  36. Hampton HR, Chtanova T. Lymphatic migration of immune cells. Front Immunol 2019; 10: 1168. doi: 10.3389/fimmu.2019.01168 PMID: 31191539
  37. König T, Nolte H, Aaltonen MJ, et al. MIROs and DRP1 drive mitochondrial-derived vesicle biogenesis and promote quality control. Nat Cell Biol 2021; 23(12): 1271-86. doi: 10.1038/s41556-021-00798-4 PMID: 34873283
  38. Park SH, Lee AR, Choi K, Joung S, Yoon JB, Kim S. TOMM20 as a potential therapeutic target of colorectal cancer. BMB Rep 2019; 52(12): 712-7. doi: 10.5483/BMBRep.2019.52.12.249 PMID: 31818360
  39. Fu ZJ, Wang ZY, Xu L, et al. HIF-1α-BNIP3-mediated mitophagy in tubular cells protects against renal ischemia/reperfusion injury. Redox Biol 2020; 36: 101671. doi: 10.1016/j.redox.2020.101671 PMID: 32829253
  40. Choong CJ, Okuno T, Ikenaka K, et al. Alternative mitochondrial quality control mediated by extracellular release. Autophagy 2021; 17(10): 2962-74. doi: 10.1080/15548627.2020.1848130 PMID: 33218272
  41. Zhou B, Zhang J, Liu X, et al. Tom20 senses iron-activated ROS signaling to promote melanoma cell pyroptosis. Cell Res 2018; 28(12): 1171-85. doi: 10.1038/s41422-018-0090-y PMID: 30287942
  42. Beyer AM, Norwood Toro LE, Hughes WE, et al. Autophagy, TERT, and mitochondrial dysfunction in hyperoxia. Am J Physiol Heart Circ Physiol 2021; 321(5): H985-H1003. doi: 10.1152/ajpheart.00166.2021 PMID: 34559580
  43. Curado S, Ober EA, Walsh S, et al. The mitochondrial import gene tomm22 is specifically required for hepatocyte survival and provides a liver regeneration model. Dis Model Mech 2010; 3(7-8): 486-95. doi: 10.1242/dmm.004390 PMID: 20483998
  44. Kravic B, Harbauer AB, Romanello V, et al. In mammalian skeletal muscle, phosphorylation of TOMM22 by protein kinase CSNK2/CK2 controls mitophagy. Autophagy 2018; 14(2): 311-35. doi: 10.1080/15548627.2017.1403716 PMID: 29165030
  45. Dou Y, Tan Y. Presequence protease reverses mitochondria‐specific amyloid‐β‐induced mitophagy to protect mitochondria. FASEB J 2023; 37(5): e22890. doi: 10.1096/fj.202200216RRRR PMID: 37002885
  46. Bertolin G, Ferrando-Miguel R, Jacoupy M, et al. The TOMM machinery is a molecular switch in PINK1 and PARK2/PARKIN-dependent mitochondrial clearance. Autophagy 2013; 9(11): 1801-17. doi: 10.4161/auto.25884 PMID: 24149440
  47. Chiba-Falek O, Gottschalk WK, Lutz MW. The effects of the TOMM40 poly‐T alleles on Alzheimer’s disease phenotypes. Alzheimers Dement 2018; 14(5): 692-8. doi: 10.1016/j.jalz.2018.01.015 PMID: 29524426
  48. Li T, Pappas C, Le ST, et al. APOE, TOMM40, and sex interactions on neural network connectivity. Neurobiol Aging 2022; 109: 158-65. doi: 10.1016/j.neurobiolaging.2021.09.020 PMID: 34740077
  49. Chen S, Sarasua SM, Davis NJ, et al. TOMM40 genetic variants associated with healthy aging and longevity: A systematic review. BMC Geriatr 2022; 22(1): 667. doi: 10.1186/s12877-022-03337-4 PMID: 35964003
  50. Lee EG, Chen S, Leong L, Tulloch J, Yu CE. TOMM40 RNA transcription in Alzheimer’s Disease brain and its implication in mitochondrial dysfunction. Genes 2021; 12(6): 871. doi: 10.3390/genes12060871 PMID: 34204109
  51. Li C, Liu J, Hou W, Kang R, Tang D. STING1 promotes ferroptosis through mfn1/2-dependent mitochondrial fusion. Front Cell Dev Biol 2021; 9: 698679. doi: 10.3389/fcell.2021.698679 PMID: 34195205
  52. Li S, Han S, Zhang Q, et al. FUNDC2 promotes liver tumorigenesis by inhibiting MFN1-mediated mitochondrial fusion. Nat Commun 2022; 13(1): 3486. doi: 10.1038/s41467-022-31187-6 PMID: 35710796
  53. Sun K, Jing X, Guo J, Yao X, Guo F. Mitophagy in degenerative joint diseases. Autophagy 2021; 17(9): 2082-92. doi: 10.1080/15548627.2020.1822097 PMID: 32967533
  54. Hu S, Kuwabara R, de Haan BJ, Smink AM, de Vos P. Acetate and butyrate improve β-cell metabolism and mitochondrial respiration under oxidative stress. Int J Mol Sci 2020; 21(4): 1542. doi: 10.3390/ijms21041542 PMID: 32102422

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