Mitochondria and ischemia reperfusion injury.
Journal
Current opinion in organ transplantation
ISSN: 1531-7013
Titre abrégé: Curr Opin Organ Transplant
Pays: United States
ID NLM: 9717388
Informations de publication
Date de publication:
01 10 2022
01 10 2022
Historique:
pubmed:
12
8
2022
medline:
16
9
2022
entrez:
11
8
2022
Statut:
ppublish
Résumé
This review describes the role of mitochondria in ischemia-reperfusion-injury (IRI). Mitochondria are the power-house of our cells and play a key role for the success of organ transplantation. With their respiratory chain, mitochondria are the main energy producers, to fuel metabolic processes, control cellular signalling and provide electrochemical integrity. The mitochondrial metabolism is however severely disturbed when ischemia occurs. Cellular energy depletes rapidly and various metabolites, including Succinate accumulate. At reperfusion, reactive oxygen species are immediately released from complex-I and initiate the IRI-cascade of inflammation. Prior to the development of novel therapies, the underlying mechanisms should be explored to target the best possible mitochondrial compound. A clinically relevant treatment should recharge energy and reduce Succinate accumulation before organ implantation. While many interventions focus instead on a specific molecule, which may inhibit downstream IRI-inflammation, mitochondrial protection can be directly achieved through hypothermic oxygenated perfusion (HOPE) before transplantation. Mitochondria are attractive targets for novel molecules to limit IRI-associated inflammation. Although dynamic preservation techniques could serve as delivery tool for new therapeutic interventions, their own inherent mechanism should not only be studied, but considered as key treatment to reduce mitochondrial injury, as seen with the HOPE-approach.
Identifiants
pubmed: 35950880
doi: 10.1097/MOT.0000000000001015
pii: 00075200-202210000-00012
doi:
Substances chimiques
Succinic Acid
AB6MNQ6J6L
Types de publication
Journal Article
Review
Langues
eng
Sous-ensembles de citation
IM
Pagination
434-445Informations de copyright
Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.
Références
Schlegel A, Porte RJ, Dutkowski P. Protective mechanisms and current clinical evidence of hypothermic oxygenated machine perfusion (HOPE) in preventing posttransplant cholangiopathy. J Hepatol 2022; 76:1330–1347.
Lonati C, Schlegel A, Battistin M, et al. Effluent molecular analysis guides liver graft allocation to clinical hypothermic oxygenated machine perfusion. Biomedicines 2021; 9:1444.
Saeb-Parsy K, Martin JL, Summers DM, et al. Mitochondria as therapeutic targets in transplantation. Trends Mol Med 2021; 27:185–198.
Teodoro JS, da Silva RT, Machado IF, et al. Shaping of hepatic ischemia/reperfusion events: the crucial role of mitochondria. Cells 2022; 11:688.
Mills EL, Kelly B, O’Neill LAJ. Mitochondria are the powerhouses of immunity. Nat Immunol 2017; 18:488–498.
Schlegel A, Muller X, Mueller M, et al. Hypothermic oxygenated perfusion protects from mitochondrial injury before liver transplantation. EBioMedicine 2020; 60:103014.
Chouchani ET, Pell VR, Gaude E, et al. Ischaemic accumulation of succinate controls reperfusion injury through mitochondrial ROS. Nature 2014; 515:431–435.
Martínez-Reyes I, Chandel NS. Mitochondrial TCA cycle metabolites control physiology and disease. Nat Commun 2020; 11:102.
Boteon YL, Laing RW, Schlegel A, et al. Combined hypothermic and normothermic machine perfusion improves functional recovery of extended criteria donor livers. Liver Transpl 2018; 24:1699–1715.
Schlegel A, Kron P, Graf R, et al. Warm vs. cold perfusion techniques to rescue rodent liver grafts. J Hepatol 2014; 61:1267–1275.
Wyss R, Méndez Carmona N, Arnold M, et al. Hypothermic, oxygenated perfusion (HOPE) provides cardioprotection via succinate oxidation prior to normothermic perfusion in a rat model of donation after circulatory death (DCD). Am J Transplant 2020; 21:1003–1011.
Galkin A, Abramov AY, Frakich N, et al. Lack of oxygen deactivates mitochondrial complex I: implications for ischemic injury? J Biol Chem 2009; 284:36055–36061.
Ansari F, Yoval-Sánchez B, Niatsetskaya Z, et al. Quantification of NADH:ubiquinone oxidoreductase (complex I) content in biological samples. J Biol Chem 2021; 297:101204.
Stegemann J, Minor T. Energy charge restoration, mitochondrial protection and reversal of preservation induced liver injury by hypothermic oxygenation prior to reperfusion. Cryobiology 2009; 58:331–336.
Westerkamp A, Karimian N, Matton A, et al. Oxygenated hypothermic machine perfusion after static cold storage improves hepatobiliary function of extended criteria donor livers. Transplantation 2016; 100:825–835.
Stepanova A, Shurubor Y, Valsecchi F, et al. Differential susceptibility of mitochondrial complex II to inhibition by oxaloacetate in brain and heart. Biochim Biophy Acta 2016; 1857:1561–1568.
Dufour S, Rousse N, Canioni P, Diolez P. Top-down control analysis of temperature effect on oxidative phosphorylation. Biochem J 1996; 314:743–751.
Schlegel A, Muller X, Dutkowski P. Hypothermic liver perfusion. Curr Opin Organ Transplant 2017; 22:563–570.
Martin J, Costa A, Gruszczyk A, et al. Succinate accumulation drives ischaemia-reperfusion injury during organ transplantation. Nat Metab 2019; 1:966–974.
Burlage L, Hessels L, van Rijn R, et al. Opposite acute potassium and sodium shifts during transplantation of hypothermic machine perfused donor livers. Am J Transplant 2018; 19:1061–1071.
Chang WJ, Chehab M, Kink S, Toledo-Pereyra LH. Intracellular calcium signaling pathways during liver ischemia and reperfusion. J Invest Surg 2010; 23:228–238.
van Golen RF, van Gulik TM, Heger M. Mechanistic overview of reactive species-induced degradation of the endothelial glycocalyx during hepatic ischemia/reperfusion injury. Free Radic Biol Med 2012; 52:1382–1402.
Murphy MP. How mitochondria produce reactive oxygen species. Biochem J 2009; 417:1–13.
Dröse S, Brandt U, Wittig I. Mitochondrial respiratory chain complexes as sources and targets of thiol-based redox-regulation. Biochim Biophys Acta 2014; 1844:1344–1354.
Zhang Q, Raoof M, Chen Y, et al. Circulating mitochondrial DAMPs cause inflammatory responses to injury. Nature 2010; 464:104–107.
Zhang J, Wang X, Vikash V, et al. ROS and ROS-mediated cellular signaling. Oxid Med Cell Longev 2016; 2016:4350965.
Tschopp J, Schroder K. NLRP3 inflammasome activation: the convergence of multiple signalling pathways on ROS production? Nat Rev Immunol 2010; 10:210–215.
Sorbara M, Girardin S. Mitochondrial ROS fuel the inflammasome. Cell Res 2011; 21:558–560.
Liu Q, Zhang D, Hu D, et al. The role of mitochondria in NLRP3 inflammasome activation. Mol Immunol 2018; 103:115–124.
Shimada K, Crother T, Karlin J, et al. Oxidized mitochondrial DNA activates the NLRP3 inflammasome during apoptosis. Immunity 2012; 36:401–414.
van Golen RF, Reiniers MJ, Marsman G, et al. The damage-associated molecular pattern HMGB1 is released early after clinical hepatic ischemia/reperfusion. Biochim Biophys Acta Mol Basis Dis 2019; 1865:1192–1200.
Longnus SL, Rutishauser N, Gillespie MN, et al. Mitochondrial damage-associated molecular patterns as potential biomarkers in DCD heart transplantation: lessons from myocardial infarction and cardiac arrest. Transplant Direct 2021; 8:1–11.
Darius T, Vergauwen M, Smith T, et al. Brief O2 uploading during continuous hypothermic machine perfusion is simple yet effective oxygenation method to improve initial kidney function in a porcine autotransplant model. Am J Transplant 2020; 20:2030–2043.
Zhao T, Mu X, You Q. Succinate: an initiator in tumorigenesis and progression. Oncotarget 2017; 8:53819–53828.
Burlage LC, Karimian N, Westerkamp AC, et al. Oxygenated hypothermic machine perfusion after static cold storage improves endothelial function of extended criteria donor livers. HPB 2017; 19:538–546.
Schlegel A, Rougemont Ode, Graf R, et al. Protective mechanisms of end-ischemic cold machine perfusion in DCD liver grafts. J Hepatol 2013; 58:278–286.
Mills EL, Kelly B, Logan A, et al. Succinate dehydrogenase supports metabolic repurposing of mitochondria to drive inflammatory macrophages. Cell 2016; 167:457.e13–470.e13.
Chouchani ET, Methner C, Nadtochiy SM, et al. Cardioprotection by S-nitrosation of a cysteine switch on mitochondrial complex I. Nat Med 2013; 19:753–759.
Xu A, Szczepanek K, Hu Y, et al. Cardioprotection by modulation of mitochondrial respiration during ischemia-reperfusion: role of apoptosis-inducing factor. Biochem Biophys Res Commun 2013; 435:627–633.
Udono H, Nishida M. Metformin-ROS-Nrf2 connection in the host defense mechanism against oxidative stress, apoptosis, cancers, and ageing. Biochim Biophys Acta Gen Subj 2022; 1866:130171.
Feng J, Wang X, Ye X, et al. Mitochondria as an important target of metformin: the mechanism of action, toxic and side effects, and new therapeutic applications. Pharmacol Res 2022; 177:106114.
Yamamoto T, Byun J, Zhai P, et al. Nicotinamide mononucleotide, an intermediate of NAD+ synthesis, protects the heart from ischemia and reperfusion. PLoS One 2014; 9:e98972.
Dare AJ, Logan A, Prime TA, et al. The mitochondria-targeted antioxidant MitoQ decreases ischemia-reperfusion injury in a murine syngeneic heart transplant model. J Heart Lung Transplant 2015; 34:1471–1480.
Genova ML, Bonacorsi E, D’Aurelio M, et al. Protective effect of exogenous coenzyme Q in rats subjected to partial hepatic ischemia and reperfusion. Biofactors 1999; 9:345–349.
James AM, Sharpley MS, Manas ARB, et al. Interaction of the mitochondria-targeted antioxidant MitoQ with phospholipid bilayers and ubiquinone oxidoreductases. J Biol Chem 2007; 282:14708–14718.
Musleh W, Bruce A, Malfroy B, Baudry M. Effects of EUK-8, a synthetic catalytic superoxide scavenger, on hypoxia- and acidosis-induced damage in hippocampal slices. Neuropharmacology 1994; 33:929–934.
Kezic A, Spasojevic I, Lezaic V, Bajcetic M. Mitochondria-targeted antioxidants: future perspectives in kidney ischemia reperfusion injury. Oxid Med Cell Longev [Internet] 2016; 2016:2950503.
Cung TT, Morel O, Cayla G, et al. Cyclosporine before PCI in patients with acute myocardial infarction. N Engl J Med 2015; 373:1021–1031.
Ottani F, Latini R, Staszewsky L, et al. Cyclosporine A in reperfused myocardial infarction: the multicenter, controlled, open-label CYCLE trial. J Am Coll Cardiol 2016; 67:365–374.
Clarke SJ, McStay GP, Halestrap AP. Sanglifehrin A acts as a potent inhibitor of the mitochondrial permeability transition and reperfusion injury of the heart by binding to cyclophilin-D at a different site from cyclosporin A. J Biol Chem 2002; 277:34793–34799.
Theruvath TP, Zhong Z, Pediaditakis P, et al. Minocycline and N -methyl-4-isoleucine cyclosporin (NIM811) mitigate storage/reperfusion injury after rat liver transplantation through suppression of the mitochondrial permeability transition. Hepatology 2008; 47:236–246.
Xu C, Wang J, Fan Z, et al. Cardioprotective effects of melatonin against myocardial ischaemia/reperfusion injury: Activation of AMPK/Nrf2 pathway. J Cell Mol Med 2021; 25:6455–6459.
Gao Y, Li ZT, Jin L, et al. Melatonin attenuates hepatic ischemia-reperfusion injury in rats by inhibiting NF-κB signaling pathway. Hepatobiliary Pancreat Dis Int 2021; 20:551–560.
Chen HH, Chen YT, Yang CC, et al. Melatonin pretreatment enhances the therapeutic effects of exogenous mitochondria against hepatic ischemia-reperfusion injury in rats through suppression of mitochondrial permeability transition. J Pineal Res 2016; 61:52–68.
Zhai M, Li B, Duan W, et al. Melatonin ameliorates myocardial ischemia reperfusion injury through SIRT3-dependent regulation of oxidative stress and apoptosis. J Pineal Res 2017; 63: doi: 10.1111/jpi.12419.
doi: 10.1111/jpi.12419
D’Amico F, Vitale A, Piovan D, et al. Use of N-acetylcysteine during liver procurement: a prospective randomized controlled study. Liver Transpl 2013; 19:135–144.
T Varela A, P Rolo A, M Palmeira C. Fatty liver and ischemia/reperfusion: are there drugs able to mitigate injury? Curr Med Chem 2011; 18:4987–5002.
Hurst S, Gonnot F, Dia M, et al. Phosphorylation of cyclophilin D at serine 191 regulates mitochondrial permeability transition pore opening and cell death after ischemia-reperfusion. Cell Death Dis 2020; 11:661.
Kaur J, Kaur T, Sharma AK, et al. Fenofibrate attenuates ischemia reperfusion-induced acute kidney injury and associated liver dysfunction in rats. Drug Dev Res 2021; 82:412–421.
Liu Z, Ye S, Zhong X, et al. Pretreatment with the ALDH2 activator Alda-1 protects rat livers from ischemia/reperfusion injury by inducing autophagy. Mol Med Rep 2020; 22:2373–2385.
Lonati C, Battistin M, Dondossola DE, et al. NDP-MSH treatment recovers marginal lungs during ex vivo lung perfusion (EVLP). Peptides (NY) 2021; 141:170552.
Lonati C, Carlin A, Leonardi P, et al. Modulatory effects of NDP-MSH in the regenerating liver after partial hepatectomy in rats. Peptides (NY) 2013; 50:145–152.
Zhang Y, Tan J, Miao Y, Zhang Q. The effect of extracellular vesicles on the regulation of mitochondria under hypoxia. Cell Death Dis 2021; 12:358.
Heineman BD, Liu X, Wu GY. Targeted mitochondrial delivery to hepatocytes: a review. J Clin Transl Hepatol 2022; 10:321–328.
Hayashida K, Takegawa R, Shoaib M, et al. Mitochondrial transplantation therapy for ischemia reperfusion injury: a systematic review of animal and human studies. J Transl Med 2021; 19:214.
Guariento A, Piekarski BL, Doulamis IP, et al. Autologous mitochondrial transplantation for cardiogenic shock in pediatric patients following ischemia-reperfusion injury. J Thorac Cardiovasc Surg 2021; 162:992–1001.
Bardallo RG, da Silva RT, Carbonell T, et al. Role of PEG35, mitochondrial ALDH2, and glutathione in cold fatty liver graft preservation: an IGL-2 approach. Int J Mol Sci 2021; 22:5332.
Shi R. Polyethylene glycol repairs membrane damage and enhances functional recovery: a tissue engineering approach to spinal cord injury. Neurosci Bull 2013; 29:460–466.
Ferrero-Andrés A, Panisello-Roselló A, Serafín A, et al. Polyethylene glycol 35 (PEG35) protects against inflammation in experimental acute necrotizing pancreatitis and associated lung injury. Int J Mol Sci 2020; 21:917.
Bejaoui M, Pantazi E, Folch-Puy E, et al. Protective effect of intravenous high molecular weight polyethylene glycol on fatty liver preservation. Biomed Res Int 2015; 2015:794287.
Teixeira da Silva R, Machado IF, Teodoro JS, et al. PEG35 as a preconditioning agent against hypoxia/reoxygenation injury. Int J Mol Sci 2022; 23:1156.
Xu X, Philip JL, Razzaque MA, et al. High-molecular-weight polyethylene glycol inhibits myocardial ischemia-reperfusion injury in vivo. J Thorac Cardiovasc Surg 2015; 149:588–593.
Alexandrino H, Varela AT, Teodoro JS, et al. Mitochondrial bioenergetics and posthepatectomy liver dysfunction. Eur J Clin Invest 2016; 46:627–635.
Sun K, Liu ZS, Sun Q. Role of mitochondria in cell apoptosis during hepatic ischemia-reperfusion injury and protective effect of ischemic postconditioning. World J Gastroenterol 2004; 10:1934–1938.
Wen M, Hu F, Gong Z, et al. HIF-1α mediates the protective effect of plasma extracellular particles induced by remote ischaemic preconditioning on oxidative stress injury in human umbilical vein endothelial cells. Exp Ther Med 2022; 23:48.
ben Mosbah I, Duval H, Mbatchi SF, et al. Intermittent selective clamping improves rat liver regeneration by attenuating oxidative and endoplasmic reticulum stress. Cell Death Dis 2014; 5:e1107.
Ricca L, Lemoine A, Cauchy F, et al. Ischemic postconditioning of the liver graft in adult liver transplantation. Transplantation 2015; 99:1633–1643.
Kim WH, Lee JH, Ko JS, et al. Effect of remote ischemic postconditioning on patients undergoing living donor liver transplantation. Liver Transpl 2014; 20:1383–1392.
Oberkofler CE, Limani P, Jang JH, et al. Systemic protection through remote ischemic preconditioning is spread by platelet-dependent signaling in mice. Hepatology 2014; 60:1409–1417.
Mergental H, Laing RW, Kirkham AJ, et al. Transplantation of discarded livers following viability testing with normothermic machine perfusion. Nat Commun 2020; 11:2939.
Gaurav R, Butler AJ, Kosmoliaptsis V, et al. Liver transplantation outcomes from controlled circulatory death donors: SCS vs in situ NRP vs ex situ NMP. Ann Surg 2022; 275:1156–1164.
Jassem W, Xystrakis E, Ghnewa Y, et al. Normothermic machine perfusion (NMP) inhibits proinflammatory responses in the liver and promotes regeneration. Hepatology 2018; 70:682–695.
European Association for the Study of the Liver E. EASL clinical practice guidelines: liver transplantation. J Hepatol 2016; 64:433–485.
Schlegel A, Foley D, Savier E, et al. Recommendations for donor and recipient selection and risk prediction: working group report from the ILTS consensus conference in DCD liver transplantation. Transplantation 2021; 105:1892–1903.
Tan YB, Pastukh VM, Gorodnya OM, et al. Enhanced mitochondrial dna repair resuscitates transplantable lungs donated after circulatory death. J Surg Res 2020; 245:273–280.
Lonati C, Bassani GA, Brambilla D, et al. Mesenchymal stem cell-derived extracellular vesicles improve the molecular phenotype of isolated rat lungs during ischemia/reperfusion injury. J Heart Lung Transplant 2019; 38:1306–1316.
Kron P, Schlegel A, Mancina L, et al. Hypothermic oxygenated perfusion (HOPE) for fatty liver grafts in rats and humans. J Hepatol 2018; 68:82–91.
Nakajima D, Chen F, Okita K, et al. Reconditioning lungs donated after cardiac death using short-term hypothermic machine perfusion. Transplantation 2012; 94:999–1004.
Prudhomme T, Kervella D, Ogbemudia AE, et al. Successful pancreas allotransplantations after hypothermic machine perfusion in a novel diabetic porcine model: a controlled study. Transpl Int 2020; 34:353–364.
Guarrera Jv, Henry SD, Samstein B, et al. Hypothermic machine preservation in human liver transplantation: the first clinical series. Am J Transplant 2010; 10:372–381.
van Rijn R, Schurink I, de Vries Y, et al. Hypothermic machine perfusion in liver transplantation — a randomized trial. N Engl J Med 2021; 384:1391–1401.
Czigany Z, Pratschke J, Froněk J, et al. Hypothermic oxygenated machine perfusion (HOPE) reduces early allograft injury and improves post-transplant outcomes in extended criteria donation (ECD) liver transplantation from donation after brain death (DBD): results from a multicenter randomized con. Ann Surg 2021; 274:705–712.
Brüggenwirth IMA, Mueller M, Lantinga VA, et al. Prolonged preservation by hypothermic machine perfusion facilitates logistics in liver transplantation: a European observational cohort study. Am J Transplant 2022; 22:1842–1851.
Pavicevic S, Uluk D, Reichelt S, et al. Hypothermic oxygenated machine perfusion for extended criteria donor allografts: preliminary experience with extended organ preservation times in the setting of organ reallocation. Artif Organs 2022; 46:306–311.
Boteon APCS, Schlegel A, Carvalho MF, Boteon YL. Hypothermic oxygenated machine perfusion as a tool to facilitate liver transplantation in the acute-on-chronic liver failure scenario. Liver Transpl 2022; doi: 10.1002/lt.26513. Online ahead of print.
doi: 10.1002/lt.26513.
Patrono D, Surra A, Catalano G, et al. Hypothermic oxygenated machine perfusion of liver grafts from brain-dead donors. Sci Rep 2019; 9:9337.
Schlegel AA, Muller X, Kalisvaart M, et al. Outcomes of liver transplantations from donation after circulatory death (DCD) treated by hypothermic oxygenated perfusion (HOPE) before implantation. J Hepatol 2019; 70:50–57.
Chen H, Lu D, Yang X, et al. One shoot, two birds: alleviating inflammation caused by ischemia/reperfusion injury to reduce the recurrence of hepatocellular carcinoma. Front Immunol 2022; 13:879552.
Li CX, Man K, Lo CM. The impact of liver graft injury on cancer recurrence posttransplantation. Transplantation 2017; 101:2665–2670.
Mueller M, Kalisvaart M, O‘Rourke J, et al. Hypothermic oxygenated liver perfusion (HOPE) prevents tumor recurrence in liver transplantation from donation after circulatory death. Ann Surg 2020; 11:759–765.
Boteon Y, Carvalho MAF, Panconesi R, et al. Preventing tumour recurrence after liver transplantation: the role of machine perfusion. Int J Mol Sci 2020; 21:5791.
Rossignol G, Muller X, Hervieu V, et al. Liver transplantation of partial grafts after ex-situ splitting during hypothermic oxygenated perfusion - the HOPE-Split pilot study. Liver Transpl 2022; doi: 10.1002/lt.26507. Online ahead of print.
doi: 10.1002/lt.26507.
Jia JJ, Xie HY, Li JH, et al. Graft protection of the liver by hypothermic machine perfusion involves recovery of graft regeneration in rats. J Int Med Res 2019; 47:427–437.
Eshmuminov D, Becker D, Bautista Borrego L, et al. An integrated perfusion machine preserves injured human livers for 1 week. Nat Biotechnol 2020; 189–198.
Clavien PA, Dutkowski P, Mueller M, et al. Transplantation of a human liver following 3 days of ex situ normothermic preservation. Nat Biotechnol 2022; doi: 10.1038/s41587-022-01354-7. Online ahead of print.
doi: 10.1038/s41587-022-01354-7.