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Antioxidant Versus Pro-Apoptotic Effects of Mushroom-Enriched Diets on Mitochondria in Liver Disease

1
Institute of Molecular Toxicology and Pharmacology, Helmholtz Center Munich, German Research Center for Environmental Health, D-85764 Neuherberg, Germany
2
CNC-Center for Neuroscience and Cell Biology, University of Coimbra, 3004-504 Coimbra, Portugal
3
DCV-Department of Life Sciences, Faculty of Sciences and Technology of the University of Coimbra, 3000-456 Coimbra, Portugal
4
IIIUC-Institute for Interdisciplinary Research, University of Coimbra, 3030-789 Coimbra, Portugal
5
Institute of Toxicology and Environmental Hygiene, Technical University Munich, D-80802 Munich, Germany
*
Author to whom correspondence should be addressed.
These authors have contributed equally, and should be considered joint first-authors.
These authors have contributed equally, and should be considered joint senior authors.
Int. J. Mol. Sci. 2019, 20(16), 3987; https://doi.org/10.3390/ijms20163987 (registering DOI)
Received: 11 July 2019 / Revised: 14 August 2019 / Accepted: 14 August 2019 / Published: 16 August 2019
(This article belongs to the Special Issue Mitochondrial Stress in Non-alcoholic Fatty Liver Disease)
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Abstract

Mitochondria play a central role in non-alcoholic fatty liver disease (NAFLD) progression and in the control of cell death signalling during the progression to hepatocellular carcinoma (HCC). Associated with the metabolic syndrome, NAFLD is mostly driven by insulin-resistant white adipose tissue lipolysis that results in an increased hepatic fatty acid influx and the ectopic accumulation of fat in the liver. Upregulation of beta-oxidation as one compensatory mechanism leads to an increase in mitochondrial tricarboxylic acid cycle flux and ATP generation. The progression of NAFLD is associated with alterations in the mitochondrial molecular composition and respiratory capacity, which increases their vulnerability to different stressors, including calcium and pro-inflammatory molecules, which result in an increased generation of reactive oxygen species (ROS) that, altogether, may ultimately lead to mitochondrial dysfunction. This may activate further pro-inflammatory pathways involved in the progression from steatosis to steatohepatitis (NASH). Mushroom-enriched diets, or the administration of their isolated bioactive compounds, have been shown to display beneficial effects on insulin resistance, hepatic steatosis, oxidative stress, and inflammation by regulating nutrient uptake and lipid metabolism as well as modulating the antioxidant activity of the cell. In addition, the gut microbiota has also been described to be modulated by mushroom bioactive molecules, with implications in reducing liver inflammation during NAFLD progression. Dietary mushroom extracts have been reported to have anti-tumorigenic properties and to induce cell-death via the mitochondrial apoptosis pathway. This calls for particular attention to the potential therapeutic properties of these natural compounds which may push the development of novel pharmacological options to treat NASH and HCC. We here review the diverse effects of mushroom-enriched diets in liver disease, emphasizing those effects that are dependent on mitochondria. View Full-Text
Keywords: mitochondria; non-alcoholic fatty liver disease; fungi; mushrooms; truffles; antioxidants; oxidative stress; lipid metabolism; apoptosis; NASH; HCC mitochondria; non-alcoholic fatty liver disease; fungi; mushrooms; truffles; antioxidants; oxidative stress; lipid metabolism; apoptosis; NASH; HCC
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Fontes, A.; Alemany-Pagès, M.; Oliveira, P.J.; Ramalho-Santos, J.; Zischka, H.; Azul, A.M. Antioxidant Versus Pro-Apoptotic Effects of Mushroom-Enriched Diets on Mitochondria in Liver Disease. Int. J. Mol. Sci. 2019, 20, 3987.

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