Diverse Functions of Autophagy in Liver Physiology and Liver Diseases

Ke, Po‐Yuan

doi:10.3390/ijms20020300

Cited by 86 publications

(62 citation statements)

References 607 publications

(776 reference statements)

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“…Autophagy is one of the pro-survival processes allowing hepatocytes to resist cellular stressors such as anoxia and nutrient starvation [112]. Autophagy protects hepatocytes from damage and cell death by clearing damaged organelles and misfolded proteins generated in hepatic disease [113].…”

Section: Autophagy Plays An Essential Role In Hepatic Physiological Pmentioning

confidence: 99%

The Role of Autophagy for the Regeneration of the Aging Liver

Hua

Tautenhahn

et al. 2020

IJMS

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Age is one of the key risk factors to develop malignant diseases leading to a high incidence of hepatic tumors in the elderly population. The only curative treatment for hepatic tumors is surgical removal, which initiates liver regeneration. However, liver regeneration is impaired with aging, leading to an increased surgical risk for the elderly patient. Due to the increased risk, those patients are potentially excluded from curative surgery. Aging impairs autophagy via lipofuscin accumulation and inhibition of autophagosome formation. Autophagy is a recycling mechanism for eukaryotic cells to maintain homeostasis. Its principal function is to degrade endogenous bio-macromolecules for recycling cellular substances. A number of recent studies have shown that the reduced regenerative capacity of the aged remnant liver can be restored by promoting autophagy. Autophagy can be activated via multiple mTOR-dependent and mTOR-independent pathways. However, inducing autophagy through the mTOR-dependent pathway alone severely impairs liver regeneration. In contrast, recent observations suggest that inducing autophagy via mTOR-independent pathways might be promising in promoting liver regeneration. Conclusion: Activation of autophagy via an mTOR-independent autophagy inducer is a potential therapy for promoting liver regeneration, especially in the elderly patients at risk.

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Section: Autophagy Plays An Essential Role In Hepatic Physiological Pmentioning

confidence: 99%

The Role of Autophagy for the Regeneration of the Aging Liver

Hua

Tautenhahn

et al. 2020

IJMS

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“…Autophagy acts as a bodyguard to protect cells, which involves concerted action to promote cell survival, for example in a state of stress when the cells are starved of nutrients or in case of a viral infection [5,10]. The importance of autophagy has been emphasized in case of CHC, since it promotes HCV persistence and suppresses the activated immune response [15].…”

Section: Discussionmentioning

confidence: 99%

“…Altered lipid metabolism is linked to the life cycle of HCV considering that virions coated with lipoproteins facilitate hepatocyte entry via lipoprotein receptors, however, the HCV-induced ER-stress leads to steatosis [ 3 ]. Intracellular lipid droplets being in excess in the cells are degraded by an autophagy process called lipophagy [ 3 – 5 , 22 ]. Vescovo et al reported that autophagy acts against the alterations in lipid metabolism induced by HCV and steatosis may develop when autophagy is disrupted [ 39 ].…”

Section: Discussionmentioning

confidence: 99%

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Autophagy, Mitophagy and MicroRNA Expression in Chronic Hepatitis C and Autoimmune Hepatitis

Szekerczés

Gógl

Illyés

et al. 2020

Pathol. Oncol. Res.

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Although the role of autophagy has been implicated in several forms of chronic hepatitis, it is still not fully understood. Active autophagy eliminates damaged molecules and organelles (such as mitochondria) by lysosomal degradation. In the present study, we aimed to examine and compare autophagy activity in chronic hepatitis C (CHC) and autoimmune hepatitis (AIH) by detecting the expression of autophagy (LC3 and p62) and mitochondrium-related (TOMM20) proteins, as well as the levels of selected microRNAs (miR-101, -155, -204 and − 224) known to be involved in the regulation of autophagy. In addition, the expression levels were related to pathohistological parameters. Liver biopsy samples, including 45 CHC and 18 AIH cases, were immunohistochemically stained for LC3, p62 and TOMM20 and the expression of miRNAs was determined using real-time PCR. We found elevated LC3 and p62 in AIH samples as compared with CHC ones, indicating an activated autophagy that is impaired in AIH as no degradation of p62 seemed to occur. Moreover, p62 showed strong correlation with necroinflammatory grades in the AIH group. The observed elevated levels of TOMM20 and p62 suggest a less efficient elimination of damaged mitochondria in AIH as opposed to CHC, in which autophagy seems to have a more active function. The level of miR-101 was increased in case of CHC as compared with AIH, however, miR-155, -204 and 224 resulted in no expressional. Furthermore, miR-224 level correlated with steatosis and miR-155 expression with fibrosis stage in CHC. In conclusion, dissimilar autophagic activity was observed in CHC and AIH, suggesting a close association between impaired autophagy and severity of necroinflammation. This impairment may not be regulated by the analyzed miRNAs. Nevertheless, miR-224 and − 155 seem to be associated with CHC progression.

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“…We found that the percentage of type1 NI with immunoposivity for p62 and cathepsin B was higher in NASH than in the controls without steatosis. The association of hepatocellular carcinogenesis with p62 is documented [38][39][40][41] . In mouse HCC models it was shown that p62 is required in progression from premalignancy www.nature.com/scientificreports/ to malignancy; high p62 expression protected HCC-initiating cells from oxidative stress-induced death 41 .…”

Section: Discussionmentioning

confidence: 99%

Characterization of two types of intranuclear hepatocellular inclusions in NAFLD

Schwertheim

Kälsch

Jastrow

et al. 2020

Sci Rep

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Nuclear inclusions (NI) are a common finding in hepatocytes from patients with liver disease especially in diabetes mellitus and non-alcoholic fatty liver disease (NAFLD) but studies examining the shape and content of these inclusions in detail are lacking. In this study we define two distinct types of NI in NAFLD: inclusions bounded by the nuclear membrane, containing degenerative cell organelles and heterolysosomes (type1) and inclusions with deposits of glycogen but without any kind of organelles and delimiting membrane (type2). NI in 77 paraffin-embedded patients of NAFLD including NAFL and non-alcoholic steatohepatitis (NASH) were analyzed. In 4–12% of type1 NI immunopositivity for the autophagy-associated proteins LC3B, ubiquitin, p62/sequestosome1, cathepsin D and cathepsin B were detected with co-localizations of ubiquitin and p62; type2 NI showed no immunoreactivity. Three-dimensional reconstructions of isolated nuclei revealed that NI type1 are completely enclosed within the nucleus, suggesting that NI, although probably derived from cytoplasmic invaginations, are not just simple invaginations. Our study demonstrates two morphologically different types of inclusions in NAFLD, whereby both gained significantly in number in advanced stages. We suggest that the presence of autophagy-associated proteins and degenerated organelles within type1 NI plays a role in disease progression.

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Diverse Functions of Autophagy in Liver Physiology and Liver Diseases

Cited by 86 publications

References 607 publications

The Role of Autophagy for the Regeneration of the Aging Liver

The Role of Autophagy for the Regeneration of the Aging Liver

Autophagy, Mitophagy and MicroRNA Expression in Chronic Hepatitis C and Autoimmune Hepatitis

Characterization of two types of intranuclear hepatocellular inclusions in NAFLD

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