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Mitochondria in Liver Diseases

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Mitochondrial Biology and Experimental Therapeutics

Abstract

Mitochondria are not only the main energy source in the hepatocytes but also play a major role in the cell redox homeostasis and maintain normal liver function including signalling pathways and the metabolism of exogenous substances. These roles assign mitochondria a gateway function in protecting hepatocyte from injury since unbalanced mitochondrial function unequivocally affects cell survival by actively causing the onset and perpetuation of liver diseases. Abnormal mitochondrial function is reported to be involved in a variety of liver diseases including drug-induced liver injury, alcoholic liver disease, non-alcoholic fatty liver disease, viral hepatitis, primary and secondary cholestasis, hemochromatosis, and Wilson’s disease. These changes lead to the impairment of the electron transport chain and/or oxidative phosphorylation, which induces a decrease in oxidative degradation of many exogenous and endogenous substrates and ATP synthesis, and in general, reduces hepatocyte tolerance towards potentially damaging insults. Structural changes accompany functional impairment of mitochondria, resulting in swelling and formation of aggregates and inclusions within the mitochondrial matrix. In chronic liver diseases, adequate mitochondrial function is maintained by mitochondrial proliferation and/or by an increased activity of critical enzymes. The assessment of mitochondrial functions in vivo is a useful tool in patients with liver diseases for diagnostic and prognostic purposes in patients with liver diseases and for the evaluation of therapeutic interventions.

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Abbreviations

ALD:

Alcoholic liver disease

AMA:

Antimitochondrial antibodies

ANG:

Angiotensin

ATP:

Adenosine triphosphate

BDL:

Bile duct ligation

ER:

Endoplasmic reticulum

Fe/S:

Iron-sulfur

GSH:

Glutathione

HFE:

Hemochromatosis gene

iNOs:

Inducible nitric oxide synthase

KGDH:

α-Ketoglutarate dehydrogenase

KICA:

α-Ketoisocaproic acid

LCFA:

Long chain fatty acids

MAM:

Mitochondria-associated membrane

MPT:

Mitochondrial permeability transition

mtDNA:

Mitochondrial DNA

NAFL:

Non-alcoholic fatty liver

NAFLD:

Non-alcoholic fatty liver disease

NASH:

Non-alcoholic steatohepatitis

NO:

Nitric oxide

PBC:

Primary biliary cirrhosis

PDH:

Pyruvate dehydrogenase

PSH:

Protein sulfhydryls

PSSG:

Protein mixed disulfides

ROS:

Reactive oxygen species

SAME:

S-Adenosyl-L-methionine

SOD:

Superoxide dismutase

TG:

Triglycerides

WD:

Wilson’s disease

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Acknowledgements

The present chapter is written in the context of the project FOIE GRAS, which has received funding from the European Union’s Horizon 2020 Research and Innovation programme under the Marie Sklodowska-Curie Grant Agreement No. 722619.

Conflicts of Interest 

We declare that we have no conflicts of interest.

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Authors and Affiliations

  1. Clinica Medica “A. Murri”, Department of Biomedical Sciences and Human Oncology, Policlinico Hospital, University of Bari Medical School, Bari, Italy

    Ignazio Grattagliano, Ornella de Bari, Domenica Di Palo & Piero Portincasa

  2. Italian College of General Practitioners, Florence, Italy

    Ignazio Grattagliano

  3. Department of Internal Medicine, First Clinic of Internal Medicine, University of Genoa, Genoa, Italy

    Fabrizio Montecucco & Federico Carbone

  4. Ospedale Policlinico San Martino, Genoa, Italy

    Fabrizio Montecucco

  5. Centre of Excellence for Biomedical Research (CEBR), University of Genoa, Genoa, Italy

    Fabrizio Montecucco

  6. CNC, Center for Neuroscience and Cell Biology, University of Coimbra, Cantanhede, Portugal

    Paulo J. Oliveira

  7. Division of Gastroenterology and Liver Diseases, Department of Medicine, Marion Bessin Liver Research Center, Albert Einstein College of Medicine, Bronx, NY, USA

    David Q.-H. Wang

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  1. Ignazio Grattagliano
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    Paulo J. Oliveira

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Grattagliano, I. et al. (2018). Mitochondria in Liver Diseases. In: Oliveira, P. (eds) Mitochondrial Biology and Experimental Therapeutics. Springer, Cham. https://doi.org/10.1007/978-3-319-73344-9_7

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