Metabolic characteristics of mitochondria in sepsis_CHINESE JOURNAL OF BASES AND CLINICS IN GENERAL SURGERY

Authors：

YUAN Gang ¹ , ZHANG Yifan ² ,  GONG Jianping ²

1. Department of Surgery, People’s Hospital of Chongqing Dadukou Area, Chongqing 400084, P. R. China;
2. Department of Hepatobiliary Surgery, The Second Affiliated Hospital of Chongqing Medical University, Chongqing 400010, P. R. China;

Corresponding author：

GONG Jianping, Email: gongjianping11@126.com

Keywords：

mitochondria; sepsis; cellular metabolism; immune response; inflammation

DOI：

10.7507/1007-9424.202203024

Video：

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Abstract Full text Figures/Tables Video References Cited by

Objective To elucidate the metabolic characteristics of mitochondria in sepsis and review its cellular mechanism, so as to provide new ideas for the treatment of sepsis. Method The previous literatures and latest research results about mitochondrial metabolism during sepsis were reviewed. Results At present, the researchers were not only concerned about the inflammatory response of sepsis, but also concerned about the systemic metabolic disorder caused by sepsis. It was believed that the damage of mitochondria caused by sepsis was one of the main reasons for the disorder of cell metabolism. During the sepsis, the patient’s metabolism had changed, for example, enhancement of aerobic glycolysis, lactic acid accumulation, elevated levels of fatty acids and triglycerides in blood, and so on. Conclusion Metabolic change during sepsis is related to mitochondria, which can provide some new methods for treatment of sepsis.

Citation： YUAN Gang, ZHANG Yifan, GONG Jianping. Metabolic characteristics of mitochondria in sepsis. CHINESE JOURNAL OF BASES AND CLINICS IN GENERAL SURGERY, 2022, 29(9): 1240-1245. doi: 10.7507/1007-9424.202203024 Copy

1.	Rudd KE, Johnson SC, Agesa KM, et al. Global, regional, and national sepsis incidence and mortality, 1990–2017: analysis for the Global Burden of Disease Study. Lancet, 2020, 395(10219): 200-211.
2.	Cohen J, Vincent JL, Adhikari NK, et al. Sepsis: a roadmap for future research. Lancet Infect Dis, 2015, 15(5): 581-614.
3.	Nunnari J, Suomalainen A. Mitochondria: in sickness and in health. Cell, 2012, 148(6): 1145-1159.
4.	van der Poll T, van de Veerdonk FL, Scicluna BP, et al. The immunopathology of sepsis and potential therapeutic targets. Nat Rev Immunol, 2017, 17(7): 407-420.
5.	Brealey D, Brand M, Hargreaves I, et al. Association between mitochondrial dysfunction and severity and outcome of septic shock. Lancet, 2002, 360(9328): 219-223.
6.	Rittirsch D, Huber-Lang MS, Flierl MA, et al. Immunodesign of experimental sepsis by cecal ligation and puncture. Nat Protoc, 2009, 4(1): 31-36.
7.	Mohr A, Polz J, Martin EM, et al. Sepsis leads to a reduced antigen-specific primary antibody response. Eur J Immunol, 2012, 42(2): 341-352.
8.	Ding Q, Qi Y, Tsang SY. Mitochondrial biogenesis, mitochondrial dynamics, and mitophagy in the maturation of cardiomyocytes. Cells, 2021, 10(9): 2463. doi: 10.3390/cells10092463.
9.	Pak ES, Uddin MJ, Ha H. Inhibition of Src family kinases ameliorates LPS-induced acute kidney injury and mitochondrial dysfunction in mice. Int J Mol Sci, 2020, 21(21): 8246. doi: 10.3390/ijms21218246.
10.	Mizushima N, Levine B, Cuervo AM, et al. Autophagy fights disease through cellular self-digestion. Nature, 2008, 451(7182): 1069-1075.
11.	Stanzani G, Duchen MR, Singer M. The role of mitochondria in sepsis-induced cardiomyopathy. Biochim Biophys Acta Mol Basis Dis, 2019, 1865(4): 759-773.
12.	Wang Y, Zhang X, Wen Y, et al. Endoplasmic reticulum-mitochondria contacts: a potential therapy target for cardiovascular remodeling-associated diseases. Front Cell Dev Biol, 2021, 9: 774989. doi: 10.3389/fcell.2021.774989.
13.	Yin X, Xin H, Mao S, et al. The role of autophagy in sepsis: protection and injury to organs. Front Physiol, 2019, 10: 1071. doi: 10.3389/fphys.2019.01071.
14.	Zhong Z, Sanchez-Lopez E, Karin M. Autophagy, inflammation, and immunity: a troika governing cancer and its treatment. Cell, 2016, 166(2): 288-298.
15.	Jin M, Liu X, Klionsky DJ. SnapShot: selective autophagy. Cell, 2013, 152(1-2): 368-368. e2. doi:10.1016/j.cell.2013.01.004.
16.	Romanello V, Sandri M. The connection between the dynamic remodeling of the mitochondrial network and the regulation of muscle mass. Cell Mol Life Sci, 2021, 78(4): 1305-1328.
17.	Liu R, Wang SC, Li M, et al. Erratum to “An inhibitor of DRP1 (Mdivi-1) alleviates LPS-induced septic AKI by inhibiting NLRP3 inflammasome activation”. Biomed Res Int, 2020, 2020: 8493938. doi: 10.1155/2020/8493938.
18.	Huang H, Xu C, Wang Y, et al. Lethal (3) malignant brain tumor-like 2 (L3MBTL2) protein protects against kidney injury by inhibiting the DNA damage-p53-apoptosis pathway in renal tubular cells. Kidney Int, 2018, 93(4): 855-870.
19.	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.
20.	Alissafi T, Kalafati L, Lazari M, et al. Mitochondrial oxidative damage underlies regulatory T cell defects in autoimmunity. Cell Metab, 2020, 32(4): 591-604.
21.	Yoo JY, Cha DR, Kim B, et al. LPS-induced acute kidney injury is mediated by Nox4-SH3YL1. Cell Rep, 2020, 33(3): 108245. doi: 10.1016/j.celrep.2020.108245.
22.	Lu QB, Du Q, Wang HP, et al. Salusin-β mediates tubular cell apoptosis in acute kidney injury: involvement of the PKC/ROS signaling pathway. Redox Biol, 2020, 30: 101411. doi: 10.1016/j.redox.2019.101411.
23.	Larrouyet-Sarto ML, Tamura AS, Alves VS, et al. P2X7 receptor deletion attenuates oxidative stress and liver damage in sepsis. Purinergic Signal, 2020, 16(4): 561-572.
24.	Díaz-Quintana A, Pérez-Mejías G, Guerra-Castellano A, et al. Wheel and deal in the mitochondrial inner membranes: the tale of cytochrome c and cardiolipin. Oxid Med Cell Longev, 2020, 2020: 6813405. doi: 10.1155/2020/6813405.
25.	Uddin MJ, Jeong J, Pak ES, et al. CO-releasing molecule-2 prevents acute kidney injury through suppression of ROS-Fyn-ER stress signaling in mouse model. Oxid Med Cell Longev, 2021, 2021: 9947772. doi: 10.1155/2021/9947772.
26.	Lin Q, Li S, Jiang N, et al. PINK1-parkin pathway of mitophagy protects against contrast-induced acute kidney injury via decreasing mitochondrial ROS and NLRP3 inflammasome activation. Redox Biol, 2019, 26: 101254. doi: 10.1016/j.redox.2019.101254.
27.	Hukriede NA, Soranno DE, Sander V, et al. Experimental models of acute kidney injury for translational research. Nat Rev Nephrol, 2022, 18(5): 277-293.
28.	Saadeh K, Fazmin IT. Mitochondrial dysfunction increases arrhythmic triggers and substrates; potential anti-arrhythmic pharmacological targets. Front Cardiovasc Med, 2021, 8: 646932. doi: 10.3389/fcvm.2021.646932.
29.	Jin YH, Li ZT, Chen H, et al. Effect of dexmedetomidine on kidney injury in sepsis rats through TLR4/MyD88/NF-κB/iNOS signaling pathway. Eur Rev Med Pharmacol Sci, 2019, 23(11): 5020-5025.
30.	Carraro M, Carrer A, Urbani A, et al. Molecular nature and regulation of the mitochondrial permeability transition pore(s), drug target(s) in cardioprotection. J Mol Cell Cardiol, 2020, 144: 76-86.
31.	Kumar S, Ashraf R, C K A. Mitochondrial dynamics regulators: implications for therapeutic intervention in cancer. Cell Biol Toxicol, 2021 Oct 18. doi: 10.1007/s10565-021-09662-5.
32.	Teixeira J, Basit F, Willems PHGM, et al. Mitochondria-targeted phenolic antioxidants induce ROS-protective pathways in primary human skin fibroblasts. Free Radic Biol Med, 2021, 163: 314-324.
33.	Federico M, De la Fuente S, Palomeque J, et al. The role of mitochondria in metabolic disease: a special emphasis on heart dysfunction. J Physiol, 2021, 599(14): 3477-3493.
34.	Morciano G, Naumova N, Koprowski P, et al. The mitochondrial permeability transition pore: an evolving concept critical for cell life and death. Biol Rev Camb Philos Soc, 2021, 96(6): 2489-2521.
35.	Nadalutti CA, Ayala-Peña S, Santos JH. Mitochondrial DNA damage as driver of cellular outcomes. Am J Physiol Cell Physiol, 2022, 322(2): C136-C150. doi: 10.1152/ajpcell.00389.2021.
36.	Liu X, Shan G. Mitochondria encoded non-coding RNAs in cell physiology. Front Cell Dev Biol, 2021, 9: 713729. doi: 10.3389/fcell.2021.713729.
37.	Han Y, Cai Y, Lai X, et al. lncRNA RMRP prevents mitochondrial dysfunction and cardiomyocyte apoptosis via the miR-1-5p/hsp70 axis in LPS-induced sepsis mice. Inflammation, 2020, 43(2): 605-618.
38.	Shan B, Li JY, Liu YJ, et al. LncRNA H19 inhibits the progression of sepsis-induced myocardial injury via regulation of the miR-93-5p/SORBS2 axis. Inflammation, 2021, 44(1): 344-357.

1. Rudd KE, Johnson SC, Agesa KM, et al. Global, regional, and national sepsis incidence and mortality, 1990–2017: analysis for the Global Burden of Disease Study. Lancet, 2020, 395(10219): 200-211.
2. Cohen J, Vincent JL, Adhikari NK, et al. Sepsis: a roadmap for future research. Lancet Infect Dis, 2015, 15(5): 581-614.
3. Nunnari J, Suomalainen A. Mitochondria: in sickness and in health. Cell, 2012, 148(6): 1145-1159.
4. van der Poll T, van de Veerdonk FL, Scicluna BP, et al. The immunopathology of sepsis and potential therapeutic targets. Nat Rev Immunol, 2017, 17(7): 407-420.
5. Brealey D, Brand M, Hargreaves I, et al. Association between mitochondrial dysfunction and severity and outcome of septic shock. Lancet, 2002, 360(9328): 219-223.
6. Rittirsch D, Huber-Lang MS, Flierl MA, et al. Immunodesign of experimental sepsis by cecal ligation and puncture. Nat Protoc, 2009, 4(1): 31-36.
7. Mohr A, Polz J, Martin EM, et al. Sepsis leads to a reduced antigen-specific primary antibody response. Eur J Immunol, 2012, 42(2): 341-352.
8. Ding Q, Qi Y, Tsang SY. Mitochondrial biogenesis, mitochondrial dynamics, and mitophagy in the maturation of cardiomyocytes. Cells, 2021, 10(9): 2463. doi: 10.3390/cells10092463.
9. Pak ES, Uddin MJ, Ha H. Inhibition of Src family kinases ameliorates LPS-induced acute kidney injury and mitochondrial dysfunction in mice. Int J Mol Sci, 2020, 21(21): 8246. doi: 10.3390/ijms21218246.
10. Mizushima N, Levine B, Cuervo AM, et al. Autophagy fights disease through cellular self-digestion. Nature, 2008, 451(7182): 1069-1075.
11. Stanzani G, Duchen MR, Singer M. The role of mitochondria in sepsis-induced cardiomyopathy. Biochim Biophys Acta Mol Basis Dis, 2019, 1865(4): 759-773.
12. Wang Y, Zhang X, Wen Y, et al. Endoplasmic reticulum-mitochondria contacts: a potential therapy target for cardiovascular remodeling-associated diseases. Front Cell Dev Biol, 2021, 9: 774989. doi: 10.3389/fcell.2021.774989.
13. Yin X, Xin H, Mao S, et al. The role of autophagy in sepsis: protection and injury to organs. Front Physiol, 2019, 10: 1071. doi: 10.3389/fphys.2019.01071.
14. Zhong Z, Sanchez-Lopez E, Karin M. Autophagy, inflammation, and immunity: a troika governing cancer and its treatment. Cell, 2016, 166(2): 288-298.
15. Jin M, Liu X, Klionsky DJ. SnapShot: selective autophagy. Cell, 2013, 152(1-2): 368-368. e2. doi:10.1016/j.cell.2013.01.004.
16. Romanello V, Sandri M. The connection between the dynamic remodeling of the mitochondrial network and the regulation of muscle mass. Cell Mol Life Sci, 2021, 78(4): 1305-1328.
17. Liu R, Wang SC, Li M, et al. Erratum to “An inhibitor of DRP1 (Mdivi-1) alleviates LPS-induced septic AKI by inhibiting NLRP3 inflammasome activation”. Biomed Res Int, 2020, 2020: 8493938. doi: 10.1155/2020/8493938.
18. Huang H, Xu C, Wang Y, et al. Lethal (3) malignant brain tumor-like 2 (L3MBTL2) protein protects against kidney injury by inhibiting the DNA damage-p53-apoptosis pathway in renal tubular cells. Kidney Int, 2018, 93(4): 855-870.
19. 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.
20. Alissafi T, Kalafati L, Lazari M, et al. Mitochondrial oxidative damage underlies regulatory T cell defects in autoimmunity. Cell Metab, 2020, 32(4): 591-604.
21. Yoo JY, Cha DR, Kim B, et al. LPS-induced acute kidney injury is mediated by Nox4-SH3YL1. Cell Rep, 2020, 33(3): 108245. doi: 10.1016/j.celrep.2020.108245.
22. Lu QB, Du Q, Wang HP, et al. Salusin-β mediates tubular cell apoptosis in acute kidney injury: involvement of the PKC/ROS signaling pathway. Redox Biol, 2020, 30: 101411. doi: 10.1016/j.redox.2019.101411.
23. Larrouyet-Sarto ML, Tamura AS, Alves VS, et al. P2X7 receptor deletion attenuates oxidative stress and liver damage in sepsis. Purinergic Signal, 2020, 16(4): 561-572.
24. Díaz-Quintana A, Pérez-Mejías G, Guerra-Castellano A, et al. Wheel and deal in the mitochondrial inner membranes: the tale of cytochrome c and cardiolipin. Oxid Med Cell Longev, 2020, 2020: 6813405. doi: 10.1155/2020/6813405.
25. Uddin MJ, Jeong J, Pak ES, et al. CO-releasing molecule-2 prevents acute kidney injury through suppression of ROS-Fyn-ER stress signaling in mouse model. Oxid Med Cell Longev, 2021, 2021: 9947772. doi: 10.1155/2021/9947772.
26. Lin Q, Li S, Jiang N, et al. PINK1-parkin pathway of mitophagy protects against contrast-induced acute kidney injury via decreasing mitochondrial ROS and NLRP3 inflammasome activation. Redox Biol, 2019, 26: 101254. doi: 10.1016/j.redox.2019.101254.
27. Hukriede NA, Soranno DE, Sander V, et al. Experimental models of acute kidney injury for translational research. Nat Rev Nephrol, 2022, 18(5): 277-293.
28. Saadeh K, Fazmin IT. Mitochondrial dysfunction increases arrhythmic triggers and substrates; potential anti-arrhythmic pharmacological targets. Front Cardiovasc Med, 2021, 8: 646932. doi: 10.3389/fcvm.2021.646932.
29. Jin YH, Li ZT, Chen H, et al. Effect of dexmedetomidine on kidney injury in sepsis rats through TLR4/MyD88/NF-κB/iNOS signaling pathway. Eur Rev Med Pharmacol Sci, 2019, 23(11): 5020-5025.
30. Carraro M, Carrer A, Urbani A, et al. Molecular nature and regulation of the mitochondrial permeability transition pore(s), drug target(s) in cardioprotection. J Mol Cell Cardiol, 2020, 144: 76-86.
31. Kumar S, Ashraf R, C K A. Mitochondrial dynamics regulators: implications for therapeutic intervention in cancer. Cell Biol Toxicol, 2021 Oct 18. doi: 10.1007/s10565-021-09662-5.
32. Teixeira J, Basit F, Willems PHGM, et al. Mitochondria-targeted phenolic antioxidants induce ROS-protective pathways in primary human skin fibroblasts. Free Radic Biol Med, 2021, 163: 314-324.
33. Federico M, De la Fuente S, Palomeque J, et al. The role of mitochondria in metabolic disease: a special emphasis on heart dysfunction. J Physiol, 2021, 599(14): 3477-3493.
34. Morciano G, Naumova N, Koprowski P, et al. The mitochondrial permeability transition pore: an evolving concept critical for cell life and death. Biol Rev Camb Philos Soc, 2021, 96(6): 2489-2521.
35. Nadalutti CA, Ayala-Peña S, Santos JH. Mitochondrial DNA damage as driver of cellular outcomes. Am J Physiol Cell Physiol, 2022, 322(2): C136-C150. doi: 10.1152/ajpcell.00389.2021.
36. Liu X, Shan G. Mitochondria encoded non-coding RNAs in cell physiology. Front Cell Dev Biol, 2021, 9: 713729. doi: 10.3389/fcell.2021.713729.
37. Han Y, Cai Y, Lai X, et al. lncRNA RMRP prevents mitochondrial dysfunction and cardiomyocyte apoptosis via the miR-1-5p/hsp70 axis in LPS-induced sepsis mice. Inflammation, 2020, 43(2): 605-618.
38. Shan B, Li JY, Liu YJ, et al. LncRNA H19 inhibits the progression of sepsis-induced myocardial injury via regulation of the miR-93-5p/SORBS2 axis. Inflammation, 2021, 44(1): 344-357.

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