Cellular endo‐lysosomal dysfunction in the pathogenesis of non‐alcoholic fatty liver disease

Du, Jinyan; Ji, Yu; Qiao, Liang; Li, Yanli; Lin, Juntang

doi:10.1111/liv.14311

Cited by 18 publications

(11 citation statements)

References 106 publications

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“…Early endosomes are the cargo originating from the uptake of extracellular material by the plasma membrane (PM), which can be transported into the PM, ER, or late endosomes. Late endosomes go into lysosomes either via direct acidification or fusion with existing lysosomes 21 . Lysosomes digest extracellular or cell-surface cargos obtained via endocytosis or degrade intracellular components via autophagy 21 .…”

Section: Organelle Interactionsmentioning

confidence: 99%

“…Late endosomes go into lysosomes either via direct acidification or fusion with existing lysosomes 21 . Lysosomes digest extracellular or cell-surface cargos obtained via endocytosis or degrade intracellular components via autophagy 21 . Both endosomes and lysosomes play an important role in endocytosis and degradation, thereby forming an endolysosomal system 22 , 23 .…”

Section: Organelle Interactionsmentioning

confidence: 99%

“…In contrast, the activation of lysosomes restores the stemness of senescent stem cells 155 . Lysosomes can originate from the direct acidification of late endosomes 21 . In this process, lysosomal enzymes are transported from the Golgi apparatus to endosomes 156 .…”

Section: The Role Of Organelle Interaction In Cellular Senescencementioning

confidence: 99%

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The relevance of organelle interactions in cellular senescence

Huang¹,

Meng²,

Wang³

et al. 2022

Theranostics

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Organelles are tiny structures with specific functions in eukaryotic cells. Since they are covered with membranes, different organelles can perform biological processes that are incompatible. Organelles can also actively communicate with each other to maintain cellular homeostasis via the vesicular trafficking pathways and membrane contact sites (MCSs), which allow the exchange of metabolites and other information required for normal cellular physiology. An imbalance in organelle interactions may result in multiple pathological processes. Growing evidence shows that abnormal organelle communication contributes to cellular senescence and is associated with organ aging. However, the key role of organelle interactions in aging has not yet been broadly reviewed and fully investigated. In this review, we summarize the role of organelle interactions in cellular senescence, and highlight their relevance for cellular calcium homeostasis, protein and lipid homeostasis, and mitochondrial quality control. Our review reveals important mechanisms of organelle interactions in cellular senescence and provides important clues for intervention strategies from a new perspective.

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Section: Organelle Interactionsmentioning

confidence: 99%

Section: Organelle Interactionsmentioning

confidence: 99%

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The relevance of organelle interactions in cellular senescence

Huang¹,

Meng²,

Wang³

et al. 2022

Theranostics

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“…Despite being understudied, research shows that lysosomal degradation plays a principal role in NAFLD pathogenesis. Key proteins of interest in lysosomal degradation are RABs (Ras-related protein Rab), Sortilin (VSP10), and SIMPLE (small integral membrane protein of lysosome/late endosome) (Strong et al, 2012;Zeigerer et al, 2012;Du et al, 2020;Song et al, 2021;Vos and van de Sluis, 2021). RABs are a large family of GTPase essential in early endosome, late endosomes, and lysosome formation.…”

Section: Lysosomal Degradation During Nafldmentioning

confidence: 99%

ER Disposal Pathways in Chronic Liver Disease: Protective, Pathogenic, and Potential Therapeutic Targets

Duwaerts

Maiers

2022

Front. Mol. Biosci.

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The endoplasmic reticulum is a central player in liver pathophysiology. Chronic injury to the ER through increased lipid content, alcohol metabolism, or accumulation of misfolded proteins causes ER stress, dysregulated hepatocyte function, inflammation, and worsened disease pathogenesis. A key adaptation of the ER to resolve stress is the removal of excess or misfolded proteins. Degradation of intra-luminal or ER membrane proteins occurs through distinct mechanisms that include ER-associated Degradation (ERAD) and ER-to-lysosome-associated degradation (ERLAD), which includes macro-ER-phagy, micro-ER-phagy, and Atg8/LC-3-dependent vesicular delivery. All three of these processes are critical for removing misfolded or unfolded protein aggregates, and re-establishing ER homeostasis following expansion/stress, which is critical for liver function and adaptation to injury. Despite playing a key role in resolving ER stress, the contribution of these degradative processes to liver physiology and pathophysiology is understudied. Analysis of publicly available datasets from diseased livers revealed that numerous genes involved in ER-related degradative pathways are dysregulated; however, their roles and regulation in disease progression are not well defined. Here we discuss the dynamic regulation of ER-related protein disposal pathways in chronic liver disease and cell-type specific roles, as well as potentially targetable mechanisms for treatment of chronic liver disease.

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“…Non-alcoholic fatty liver disease (NAFLD) is a spectrum of chronic diseases that includes fatty liver disease, steatosis, and more aggressive lesions such as steatohepatitis, lobular necro-inflammation with fibrosis, or cirrhosis [ [1] , [2] , [3] ]. NAFLD is often caused by obesity or lifestyle-related diseases, and it is classified into simple fatty liver and nonalcoholic steatohepatitis (NASH) [ 4 ].…”

Section: Introductionmentioning

confidence: 99%

Dantrolene prevents hepatic steatosis by reducing cytoplasmic Ca2+ level and ER stress

Tamitani

Yamamoto

et al. 2020

Biochemistry and Biophysics Reports

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Introduction Our previous studies demonstrated that dantrolene, a ryanodine receptor stabilizer, prevents endoplasmic reticulum (ER) stress in the heart. ER stress is a strong mediator of impaired lipid metabolism in the liver, thereby contributing to fatty liver disease. In this study, we investigated the effects of dantrolene on fatty liver disease in mice and ER stress in hepatocytes. Methods and results Eight weeks old C57BL/6 mice were fed high-fat diet (HFD) for 8 weeks with or without the oral administration of dantrolene (100 mg/kg/day). The livers of mice without dantrolene (HFD group) showed severe fatty liver, whereas the livers of the mice treated with dantrolene (HFD + DAN group) only showed slightly fatty liver. To address the preventive effects of dantrolene, primary hepatocytes were cultured with palmitate in the presence or absence of dantrolene. Dantrolene reduced lipid load and prevents palmitate-induced increase in cytoplasmic Ca 2+ and ER stress. Based on these findings, we propose that dantrolene is a potential new therapeutic agent against fatty liver disease.

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Cellular endo‐lysosomal dysfunction in the pathogenesis of non‐alcoholic fatty liver disease

Cited by 18 publications

References 106 publications

The relevance of organelle interactions in cellular senescence

The relevance of organelle interactions in cellular senescence

ER Disposal Pathways in Chronic Liver Disease: Protective, Pathogenic, and Potential Therapeutic Targets

Dantrolene prevents hepatic steatosis by reducing cytoplasmic Ca2+ level and ER stress

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