Relevance of autophagy in parenchymal and non-parenchymal liver cells for health and disease

Ralf Weiskirchen, Frank Tacke

Research output: Contribution to journalReview articlepeer-review

45 Scopus citations

Abstract

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.

Original languageEnglish
Article number16
JournalCells
Volume8
Issue number1
DOIs
StatePublished - 1 Jan 2019
Externally publishedYes

Keywords

  • Biomarkers
  • Cirrhosis
  • Fibrosis
  • Hepatic stellate cells
  • Hepatocellular carcinoma
  • Hepatocytes
  • Macrophages
  • Sinusoidal endothelial cells

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