Relevance of Autophagy in Parenchymal and Non-Parenchymal Liver Cells for Health and Disease
Autophagy is a highly conserved intracellular process for the ordered degradation and recycling of cellular components in lysosomes. In the liver, parenchymal cells (i.e., mainly hepatocytes) utilize autophagy to provide amino acids, glucose, and free fatty acids as sources of energy and biosynthesi...
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| Format: | Article |
| Language: | English |
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MDPI AG
2019-01-01
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| Series: | Cells |
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| Online Access: | http://www.mdpi.com/2073-4409/8/1/16 |
| _version_ | 1797709841008951296 |
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| author | Ralf Weiskirchen Frank Tacke |
| author_facet | Ralf Weiskirchen Frank Tacke |
| author_sort | Ralf Weiskirchen |
| collection | DOAJ |
| description | Autophagy is a highly conserved intracellular process for the ordered degradation and recycling of cellular components in lysosomes. In the liver, parenchymal cells (i.e., mainly hepatocytes) utilize autophagy to provide amino acids, glucose, and free fatty acids as sources of energy and biosynthesis functions, but also for recycling and controlling organelles such as mitochondria. Non-parenchymal cells of the liver, including endothelial cells, macrophages (Kupffer cells), and hepatic stellate cells (HSC), also employ autophagy, either for maintaining cellular homeostasis (macrophages, endothelium) or for providing energy for their activation (stellate cells). In hepatocytes, autophagy contributes to essential homeostatic functions (e.g., gluconeogenesis, glycogenolysis, fatty acid oxidation), but is also implicated in diseases. For instance, storage disorders (alpha 1 antitrypsin deficiency, Wilson’s disease), metabolic (non-alcoholic steatohepatitis, NASH), and toxic (alcohol) liver diseases may benefit from augmenting autophagy in hepatocytes. In hepatic fibrosis, autophagy has been implicated in the fibrogenic activation of HSC to collagen-producing myofibroblasts. In hepatocellular carcinoma (HCC), autophagy may contribute to tumor surveillance as well as invasiveness, indicating a dual and stage-dependent function in cancer. As many drugs directly or indirectly modulate autophagy, it is intriguing to investigate autophagy-targeting, possibly even cell type-directed strategies for the treatment of hereditary liver diseases, NASH, fibrosis, and HCC. |
| first_indexed | 2024-03-12T06:42:43Z |
| format | Article |
| id | doaj.art-dba7993d69e14d1fa625bf5f442b0cbf |
| institution | Directory Open Access Journal |
| issn | 2073-4409 |
| language | English |
| last_indexed | 2024-03-12T06:42:43Z |
| publishDate | 2019-01-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Cells |
| spelling | doaj.art-dba7993d69e14d1fa625bf5f442b0cbf2023-09-03T00:54:29ZengMDPI AGCells2073-44092019-01-01811610.3390/cells8010016cells8010016Relevance of Autophagy in Parenchymal and Non-Parenchymal Liver Cells for Health and DiseaseRalf Weiskirchen0Frank Tacke1Institute of Molecular Pathobiochemistry, Experimental Gene Therapy and Clinical Chemistry, University Hospital RWTH Aachen, D-52074 Aachen, GermanyDepartment of Medicine III, University Hospital RWTH Aachen, D-52074 Aachen, GermanyAutophagy is a highly conserved intracellular process for the ordered degradation and recycling of cellular components in lysosomes. In the liver, parenchymal cells (i.e., mainly hepatocytes) utilize autophagy to provide amino acids, glucose, and free fatty acids as sources of energy and biosynthesis functions, but also for recycling and controlling organelles such as mitochondria. Non-parenchymal cells of the liver, including endothelial cells, macrophages (Kupffer cells), and hepatic stellate cells (HSC), also employ autophagy, either for maintaining cellular homeostasis (macrophages, endothelium) or for providing energy for their activation (stellate cells). In hepatocytes, autophagy contributes to essential homeostatic functions (e.g., gluconeogenesis, glycogenolysis, fatty acid oxidation), but is also implicated in diseases. For instance, storage disorders (alpha 1 antitrypsin deficiency, Wilson’s disease), metabolic (non-alcoholic steatohepatitis, NASH), and toxic (alcohol) liver diseases may benefit from augmenting autophagy in hepatocytes. In hepatic fibrosis, autophagy has been implicated in the fibrogenic activation of HSC to collagen-producing myofibroblasts. In hepatocellular carcinoma (HCC), autophagy may contribute to tumor surveillance as well as invasiveness, indicating a dual and stage-dependent function in cancer. As many drugs directly or indirectly modulate autophagy, it is intriguing to investigate autophagy-targeting, possibly even cell type-directed strategies for the treatment of hereditary liver diseases, NASH, fibrosis, and HCC.http://www.mdpi.com/2073-4409/8/1/16hepatocyteshepatic stellate cellssinusoidal endothelial cellsmacrophagesfibrosiscirrhosishepatocellular carcinomabiomarkers |
| spellingShingle | Ralf Weiskirchen Frank Tacke Relevance of Autophagy in Parenchymal and Non-Parenchymal Liver Cells for Health and Disease Cells hepatocytes hepatic stellate cells sinusoidal endothelial cells macrophages fibrosis cirrhosis hepatocellular carcinoma biomarkers |
| title | Relevance of Autophagy in Parenchymal and Non-Parenchymal Liver Cells for Health and Disease |
| title_full | Relevance of Autophagy in Parenchymal and Non-Parenchymal Liver Cells for Health and Disease |
| title_fullStr | Relevance of Autophagy in Parenchymal and Non-Parenchymal Liver Cells for Health and Disease |
| title_full_unstemmed | Relevance of Autophagy in Parenchymal and Non-Parenchymal Liver Cells for Health and Disease |
| title_short | Relevance of Autophagy in Parenchymal and Non-Parenchymal Liver Cells for Health and Disease |
| title_sort | relevance of autophagy in parenchymal and non parenchymal liver cells for health and disease |
| topic | hepatocytes hepatic stellate cells sinusoidal endothelial cells macrophages fibrosis cirrhosis hepatocellular carcinoma biomarkers |
| url | http://www.mdpi.com/2073-4409/8/1/16 |
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