Mitochondria-meditated pathways of organ failure upon inflammation
Liver failure induced by systemic inflammatory response (SIRS) is often associated with mitochondrial dysfunction but the mechanism linking SIRS and mitochondria-mediated liver failure is still a matter of discussion. Current hypotheses suggest that causative events could be a drop in ATP synthesis,...
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| Format: | Article |
| Language: | English |
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Elsevier
2017-10-01
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| Series: | Redox Biology |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2213231717302495 |
| _version_ | 1830477712458776576 |
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| author | Andrey V. Kozlov Jack R. Lancaster, Jr. Andras T. Meszaros Adelheid Weidinger |
| author_facet | Andrey V. Kozlov Jack R. Lancaster, Jr. Andras T. Meszaros Adelheid Weidinger |
| author_sort | Andrey V. Kozlov |
| collection | DOAJ |
| description | Liver failure induced by systemic inflammatory response (SIRS) is often associated with mitochondrial dysfunction but the mechanism linking SIRS and mitochondria-mediated liver failure is still a matter of discussion. Current hypotheses suggest that causative events could be a drop in ATP synthesis, opening of mitochondrial permeability transition pore, specific changes in mitochondrial morphology, impaired Ca2+ uptake, generation of mitochondrial reactive oxygen species (mtROS), turnover of mitochondria and imbalance in electron supply to the respiratory chain. The aim of this review is to critically analyze existing hypotheses, in order to highlight the most promising research lines helping to prevent liver failure induced by SIRS. Evaluation of the literature shows that there is no consistent support that impaired Ca++ metabolism, electron transport chain function and ultrastructure of mitochondria substantially contribute to liver failure. Moreover, our analysis suggests that the drop in ATP levels has protective rather than a deleterious character. Recent data suggest that the most critical mitochondrial event occurring upon SIRS is the release of mtROS in cytoplasm, which can activate two specific intracellular signaling cascades. The first is the mtROS-mediated activation of NADPH-oxidase in liver macrophages and endothelial cells; the second is the acceleration of the expression of inflammatory genes in hepatocytes. The signaling action of mtROS is strictly controlled in mitochondria at three points, (i) at the site of ROS generation at complex I, (ii) the site of mtROS release in cytoplasm via permeability transition pore, and (iii) interaction with specific kinases in cytoplasm. The systems controlling mtROS-signaling include pro- and anti-inflammatory mediators, nitric oxide, Ca2+ and NADPH-oxidase. Analysis of the literature suggests that further research should be focused on the impact of mtROS on organ failure induced by inflammation and simultaneously providing a new theoretical basis for a targeted therapy of overwhelmed inflammatory response. |
| first_indexed | 2024-12-21T16:18:34Z |
| format | Article |
| id | doaj.art-1085360704a14654a6d50568c369d85c |
| institution | Directory Open Access Journal |
| issn | 2213-2317 |
| language | English |
| last_indexed | 2024-12-21T16:18:34Z |
| publishDate | 2017-10-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Redox Biology |
| spelling | doaj.art-1085360704a14654a6d50568c369d85c2022-12-21T18:57:38ZengElsevierRedox Biology2213-23172017-10-0113C17018110.1016/j.redox.2017.05.017Mitochondria-meditated pathways of organ failure upon inflammationAndrey V. Kozlov0Jack R. Lancaster, Jr.1Andras T. Meszaros2Adelheid Weidinger3Ludwig Boltzmann Institute for Experimental and Clinical Traumatology, AUVA Research Center, Donaueschingen Str. 13, 1200 Vienna, AustriaUniversity of Pittsburgh, Departments of Pharmacology & Chemical Biology, Surgery, and Medicine, 1341A Thomas E. Starzl Biomedical Science Tower, PA 15261, United StatesUniversity of Szeged, Institute of Surgical Research, 6720 Szeged, HungaryLudwig Boltzmann Institute for Experimental and Clinical Traumatology, AUVA Research Center, Donaueschingen Str. 13, 1200 Vienna, AustriaLiver failure induced by systemic inflammatory response (SIRS) is often associated with mitochondrial dysfunction but the mechanism linking SIRS and mitochondria-mediated liver failure is still a matter of discussion. Current hypotheses suggest that causative events could be a drop in ATP synthesis, opening of mitochondrial permeability transition pore, specific changes in mitochondrial morphology, impaired Ca2+ uptake, generation of mitochondrial reactive oxygen species (mtROS), turnover of mitochondria and imbalance in electron supply to the respiratory chain. The aim of this review is to critically analyze existing hypotheses, in order to highlight the most promising research lines helping to prevent liver failure induced by SIRS. Evaluation of the literature shows that there is no consistent support that impaired Ca++ metabolism, electron transport chain function and ultrastructure of mitochondria substantially contribute to liver failure. Moreover, our analysis suggests that the drop in ATP levels has protective rather than a deleterious character. Recent data suggest that the most critical mitochondrial event occurring upon SIRS is the release of mtROS in cytoplasm, which can activate two specific intracellular signaling cascades. The first is the mtROS-mediated activation of NADPH-oxidase in liver macrophages and endothelial cells; the second is the acceleration of the expression of inflammatory genes in hepatocytes. The signaling action of mtROS is strictly controlled in mitochondria at three points, (i) at the site of ROS generation at complex I, (ii) the site of mtROS release in cytoplasm via permeability transition pore, and (iii) interaction with specific kinases in cytoplasm. The systems controlling mtROS-signaling include pro- and anti-inflammatory mediators, nitric oxide, Ca2+ and NADPH-oxidase. Analysis of the literature suggests that further research should be focused on the impact of mtROS on organ failure induced by inflammation and simultaneously providing a new theoretical basis for a targeted therapy of overwhelmed inflammatory response.http://www.sciencedirect.com/science/article/pii/S2213231717302495Liver failureMitochondriaReactive oxygen speciesSignalingInflammation |
| spellingShingle | Andrey V. Kozlov Jack R. Lancaster, Jr. Andras T. Meszaros Adelheid Weidinger Mitochondria-meditated pathways of organ failure upon inflammation Redox Biology Liver failure Mitochondria Reactive oxygen species Signaling Inflammation |
| title | Mitochondria-meditated pathways of organ failure upon inflammation |
| title_full | Mitochondria-meditated pathways of organ failure upon inflammation |
| title_fullStr | Mitochondria-meditated pathways of organ failure upon inflammation |
| title_full_unstemmed | Mitochondria-meditated pathways of organ failure upon inflammation |
| title_short | Mitochondria-meditated pathways of organ failure upon inflammation |
| title_sort | mitochondria meditated pathways of organ failure upon inflammation |
| topic | Liver failure Mitochondria Reactive oxygen species Signaling Inflammation |
| url | http://www.sciencedirect.com/science/article/pii/S2213231717302495 |
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