Mitochondrial Dysfunction in Advanced Liver Disease: Emerging Concepts

Mitochondria are entrusted with the challenging task of providing energy through the generation of ATP, the universal cellular currency, thereby being highly flexible to different acute and chronic nutrient demands of the cell. The fact that mitochondrial diseases (genetic disorders caused by mutati...

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Autores principales:	Ingrid W. Zhang, Cristina López-Vicario, Marta Duran-Güell, Joan Clària
Formato:	article
Lenguaje:	EN
Publicado:	Frontiers Media S.A. 2021
Materias:	mitochondrial dysfunction systemic inflammation organ failure cirrhosis acute decompensation immunometabolism Biology (General) QH301-705.5
Acceso en línea:	https://doaj.org/article/98a1b6af0b7645aea364efe9bc4f7f68
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spelling	oai:doaj.org-article:98a1b6af0b7645aea364efe9bc4f7f682021-11-30T13:28:00ZMitochondrial Dysfunction in Advanced Liver Disease: Emerging Concepts2296-889X10.3389/fmolb.2021.772174https://doaj.org/article/98a1b6af0b7645aea364efe9bc4f7f682021-11-01T00:00:00Zhttps://www.frontiersin.org/articles/10.3389/fmolb.2021.772174/fullhttps://doaj.org/toc/2296-889XMitochondria are entrusted with the challenging task of providing energy through the generation of ATP, the universal cellular currency, thereby being highly flexible to different acute and chronic nutrient demands of the cell. The fact that mitochondrial diseases (genetic disorders caused by mutations in the nuclear or mitochondrial genome) manifest through a remarkable clinical variation of symptoms in affected individuals underlines the far-reaching implications of mitochondrial dysfunction. The study of mitochondrial function in genetic or non-genetic diseases therefore requires a multi-angled approach. Taking into account that the liver is among the organs richest in mitochondria, it stands to reason that in the process of unravelling the pathogenesis of liver-related diseases, researchers give special focus to characterizing mitochondrial function. However, mitochondrial dysfunction is not a uniformly defined term. It can refer to a decline in energy production, increase in reactive oxygen species and so forth. Therefore, any study on mitochondrial dysfunction first needs to define the dysfunction to be investigated. Here, we review the alterations of mitochondrial function in liver cirrhosis with emphasis on acutely decompensated liver cirrhosis and acute-on-chronic liver failure (ACLF), the latter being a form of acute decompensation characterized by a generalized state of systemic hyperinflammation/immunosuppression and high mortality rate. The studies that we discuss were either carried out in liver tissue itself of these patients, or in circulating leukocytes, whose mitochondrial alterations might reflect tissue and organ mitochondrial dysfunction. In addition, we present different methodological approaches that can be of utility to address the diverse aspects of hepatocyte and leukocyte mitochondrial function in liver disease. They include assays to measure metabolic fluxes using the comparatively novel Biolog’s MitoPlates in a 96-well format as well as assessment of mitochondrial respiration by high-resolution respirometry using Oroboros’ O2k-technology and Agilent Seahorse XF technology.Ingrid W. ZhangIngrid W. ZhangCristina López-VicarioCristina López-VicarioCristina López-VicarioMarta Duran-GüellMarta Duran-GüellJoan ClàriaJoan ClàriaJoan ClàriaJoan ClàriaFrontiers Media S.A.articlemitochondrial dysfunctionsystemic inflammationorgan failurecirrhosisacute decompensationimmunometabolismBiology (General)QH301-705.5ENFrontiers in Molecular Biosciences, Vol 8 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	mitochondrial dysfunction systemic inflammation organ failure cirrhosis acute decompensation immunometabolism Biology (General) QH301-705.5
spellingShingle	mitochondrial dysfunction systemic inflammation organ failure cirrhosis acute decompensation immunometabolism Biology (General) QH301-705.5 Ingrid W. Zhang Ingrid W. Zhang Cristina López-Vicario Cristina López-Vicario Cristina López-Vicario Marta Duran-Güell Marta Duran-Güell Joan Clària Joan Clària Joan Clària Joan Clària Mitochondrial Dysfunction in Advanced Liver Disease: Emerging Concepts
description	Mitochondria are entrusted with the challenging task of providing energy through the generation of ATP, the universal cellular currency, thereby being highly flexible to different acute and chronic nutrient demands of the cell. The fact that mitochondrial diseases (genetic disorders caused by mutations in the nuclear or mitochondrial genome) manifest through a remarkable clinical variation of symptoms in affected individuals underlines the far-reaching implications of mitochondrial dysfunction. The study of mitochondrial function in genetic or non-genetic diseases therefore requires a multi-angled approach. Taking into account that the liver is among the organs richest in mitochondria, it stands to reason that in the process of unravelling the pathogenesis of liver-related diseases, researchers give special focus to characterizing mitochondrial function. However, mitochondrial dysfunction is not a uniformly defined term. It can refer to a decline in energy production, increase in reactive oxygen species and so forth. Therefore, any study on mitochondrial dysfunction first needs to define the dysfunction to be investigated. Here, we review the alterations of mitochondrial function in liver cirrhosis with emphasis on acutely decompensated liver cirrhosis and acute-on-chronic liver failure (ACLF), the latter being a form of acute decompensation characterized by a generalized state of systemic hyperinflammation/immunosuppression and high mortality rate. The studies that we discuss were either carried out in liver tissue itself of these patients, or in circulating leukocytes, whose mitochondrial alterations might reflect tissue and organ mitochondrial dysfunction. In addition, we present different methodological approaches that can be of utility to address the diverse aspects of hepatocyte and leukocyte mitochondrial function in liver disease. They include assays to measure metabolic fluxes using the comparatively novel Biolog’s MitoPlates in a 96-well format as well as assessment of mitochondrial respiration by high-resolution respirometry using Oroboros’ O2k-technology and Agilent Seahorse XF technology.
format	article
author	Ingrid W. Zhang Ingrid W. Zhang Cristina López-Vicario Cristina López-Vicario Cristina López-Vicario Marta Duran-Güell Marta Duran-Güell Joan Clària Joan Clària Joan Clària Joan Clària
author_facet	Ingrid W. Zhang Ingrid W. Zhang Cristina López-Vicario Cristina López-Vicario Cristina López-Vicario Marta Duran-Güell Marta Duran-Güell Joan Clària Joan Clària Joan Clària Joan Clària
author_sort	Ingrid W. Zhang
title	Mitochondrial Dysfunction in Advanced Liver Disease: Emerging Concepts
title_short	Mitochondrial Dysfunction in Advanced Liver Disease: Emerging Concepts
title_full	Mitochondrial Dysfunction in Advanced Liver Disease: Emerging Concepts
title_fullStr	Mitochondrial Dysfunction in Advanced Liver Disease: Emerging Concepts
title_full_unstemmed	Mitochondrial Dysfunction in Advanced Liver Disease: Emerging Concepts
title_sort	mitochondrial dysfunction in advanced liver disease: emerging concepts
publisher	Frontiers Media S.A.
publishDate	2021
url	https://doaj.org/article/98a1b6af0b7645aea364efe9bc4f7f68
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Mitochondrial Dysfunction in Advanced Liver Disease: Emerging Concepts

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