Abstract:
:Macroautophagy/autophagy is critical in maintaining cellular functions and homeostasis. Dynamic regulation of autophagy is associated with development of nonalcoholic fatty liver disease (NAFLD) and nonalcoholic steatohepatitis (NASH); however, the mechanisms involved in the regulation of autophagy in NAFLD/NASH are not well understood. Here we discuss our recent work identifying MLKL as an important nexus between autophagy and necroptosis in models of NAFLD/NASH. Mlkl, but not Ripk3, deficiency protects mice from Western diet-induced liver injury. Mlkl deficiency also prevents the accumulation of SQSTM1/p62 and LC3-II in liver in response to Western diet feeding or challenge with the protease inhibitor leupeptin. Western diet increases expression, phosphorylation and oligomerization of MLKL. In hepatocytes, palmitic acid (PA) induces the expression and translocation of MLKL to autophagosomes prior to the plasma membrane. Importantly, Mlkl, but not Ripk3, deficiency prevents the inhibition of autophagy by PA or chloroquine in hepatocytes. In contrast, overexpression of Mlkl blocks autophagic flux. Importantly, inhibition of autophagy by leupeptin or chloroquine triggers MLKL translocation to the plasma membrane, suggesting that MLKL is intimately involved in the regulation of autophagy under multiple conditions. These data indicate that MLKL contributes to Western diet-induced liver injury through inhibition of autophagy and induction of necroptosis.
journal_name
Autophagyjournal_title
Autophagyauthors
Wu X,Nagy LEdoi
10.1080/15548627.2020.1760624subject
Has Abstractpub_date
2020-07-01 00:00:00pages
1351-1352issue
7eissn
1554-8627issn
1554-8635journal_volume
16pub_type
杂志文章相关文献
Autophagy文献大全abstract::Autophagy is essential for prolonging yeast survival during nutrient deprivation; however, this report shows that some autophagy proteins may also be accelerating population death in those conditions. While leucine starvation caused YCA1-mediated apoptosis characterized by increased annexin V staining, nitrogen depriv...
journal_title:Autophagy
pub_type: 杂志文章
doi:10.4161/auto.19314
更新日期:2012-05-01 00:00:00
abstract::Autophagy is a highly conserved homeostatic pathway that plays an important role in tumor development and progression by acting on cancer cells in a cell-autonomous mechanism. However, the solid tumor is not an island, but rather an ensemble performance that includes nonmalignant stromal cells, such as macrophages. A ...
journal_title:Autophagy
pub_type: 杂志文章,评审
doi:10.4161/auto.26927
更新日期:2014-02-01 00:00:00
abstract::The accumulation of ubiquitin-positive protein aggregates has been implicated in the pathogenesis of neurodegenerative diseases, heart disease and diabetes. Emerging evidence indicates that the autophagy lysosomal pathway plays a critical role in the clearance of ubiquitin aggregates, a process that is mediated by the...
journal_title:Autophagy
pub_type: 杂志文章
doi:10.4161/auto.6.5.12189
更新日期:2010-07-01 00:00:00
abstract::Ubiquitin-proteasome system and autophagy are the two major mechanisms for protein degradation in eukaryotic cells. LC3, a ubiquitin-like protein, plays an essential role in autophagy through its ability to be conjugated to phosphatidylethanolamine. In this study, we discovered a novel LC3-processing activity, and bio...
journal_title:Autophagy
pub_type: 杂志文章
doi:10.4161/auto.6.1.10928
更新日期:2010-01-01 00:00:00
abstract::Hepatocellular carcinoma (HCC) is the consequence of chronic liver damage caused by the excessive generation of reactive oxygen species (ROS). To mitigate the deleterious effects of ROS, cells activate the transcription factor NFE2L2/NRF2, which is constitutively degraded through its partner KEAP1. The inactivation of...
journal_title:Autophagy
pub_type: 评论,杂志文章
doi:10.1080/15548627.2020.1797290
更新日期:2020-10-01 00:00:00
abstract::Flies expressing the most common Parkinson disease (PD)-related mutation, LRRK2-G2019S, in their dopaminergic neurons show loss of visual function and degeneration of the retina, including mitochondrial abnormalities, apoptosis and autophagy. Since the photoreceptors that degenerate are not dopaminergic, this demonstr...
journal_title:Autophagy
pub_type: 杂志文章
doi:10.4161/auto.24397
更新日期:2013-06-01 00:00:00
abstract::As a selective degradation system, chaperone-mediated autophagy (CMA) is essential for maintaining cellular homeostasis and survival under stress conditions. Increasing evidence points to an important role for the dysfunction of CMA in the pathogenesis of Parkinson disease (PD). However, the mechanisms by which CMA re...
journal_title:Autophagy
pub_type: 杂志文章
doi:10.1080/15548627.2016.1179401
更新日期:2016-08-02 00:00:00
abstract::Earlier studies have shown that macroautophagy is not a constitutively activated process, however, the mechanism of activation is not fully understood. Here, we report that autophagy is a dynamic process in cancer cells in response to glucose starvation. In addition, we determined that FOXO1 turnover is involved in th...
journal_title:Autophagy
pub_type: 杂志文章
doi:10.4161/auto.23918
更新日期:2013-05-01 00:00:00
abstract::We detail here a protocol using tandem-tagged mCherry-EGFP-LC3 (C-G-LC3) to quantify autophagic flux in single cells by ratiometric flow cytometry and to isolate subpopulations of cells based on their relative levels of autophagic flux. This robust and sensitive method measures autophagic flux rather than autophagosom...
journal_title:Autophagy
pub_type: 杂志文章
doi:10.4161/auto.29394
更新日期:2014-07-01 00:00:00
abstract::Multiple stress pathways result in the induction of autophagy and apoptosis. Current methods (e.g., protein gel blot, microscopy) do not offer quantitative single-cell resolution, thus making it difficult to discern if these pathways are mutually exclusive or, in some situations, cooperative in executing cell death. W...
journal_title:Autophagy
pub_type: 杂志文章
doi:10.4161/auto.7.9.16252
更新日期:2011-09-01 00:00:00
abstract::The vascular system of plants consists of two conducting tissues, xylem and phloem, which differentiate from procambium cells. Xylem serves as a transporting system for water and signaling molecules and is formed by sequential developmental processes, including cell division/expansion, secondary cell wall deposition, ...
journal_title:Autophagy
pub_type: 杂志文章
doi:10.4161/auto.6.8.13429
更新日期:2010-11-01 00:00:00
abstract::Hyperactivation of mechanistic target of rapamycin (MTOR) is a common feature of human cancers, and MTOR inhibitors, such as rapamycin, are thus becoming therapeutics in targeting certain cancers. However, rapamycin has also been found to compromise the efficacy of chemotherapeutics to cells with hyperactive MTOR. Her...
journal_title:Autophagy
pub_type: 杂志文章
doi:10.4161/auto.26447
更新日期:2013-12-01 00:00:00
abstract::Autophagy and microRNA (miRNA) are important regulators during cancer cell tumorigenesis. Impaired autophagy and high expression of the oncogenic microRNA MIR224 are prevalent in hepatocellular carcinoma (HCC); however, the relationship between the 2 phenomena remains elusive. In this study, we are the first to reveal...
journal_title:Autophagy
pub_type: 杂志文章
doi:10.4161/auto.29959
更新日期:2014-09-01 00:00:00
abstract::Macroautophagy sequesters superflous cytosol and organelles into double-membraned autophagosomes. Over 30 autophagy-related (ATG) genes have been identified without elucidating the molecular details of autophagosome biogenesis. All proposed models for autophagosome formation require membrane fusion events (Fig. 1). Pr...
journal_title:Autophagy
pub_type: 杂志文章
doi:10.4161/auto.7.2.14383
更新日期:2011-02-01 00:00:00
abstract::The lack of a rapid and quantitative autophagy assay has substantially hindered the development and implementation of autophagy-targeting therapies for a variety of human diseases. To address this critical issue, we developed a novel autophagy assay using the newly developed Cyto-ID fluorescence dye. We first verified...
journal_title:Autophagy
pub_type: 杂志文章
doi:10.1080/15548627.2015.1017181
更新日期:2015-01-01 00:00:00
abstract::The Pacific oyster, Crassostrea gigas, is a mollusk bivalve commercially important as a food source. Pacific oysters are subjected to stress and diseases during culture. The autophagy pathway is involved in numerous cellular processes, including responses to starvation, cell death, and microorganism elimination. Autop...
journal_title:Autophagy
pub_type: 杂志文章
doi:10.1080/15548627.2020.1713643
更新日期:2020-11-01 00:00:00
abstract::To examine the functional significance and detailed morphological characteristics of starvation-induced autophagy in the adult heart, we starved green fluorescent protein (GFP)-microtubule-associated protein 1 light chain 3 (LC3) transgenic mice for up to 3 days. Electron microscopy revealed that, after as little as 1...
journal_title:Autophagy
pub_type: 杂志文章
doi:10.4161/auto.5.7.9297
更新日期:2009-10-01 00:00:00
abstract::Rapamycin is an inhibitor of mTOR, a key component of the mTORC1 complex that controls the growth and survival of cells in response to growth factors, nutrients, energy balance and stresses. The downstream targets of mTORC1 include ribosome biogenesis, transcription, translation and macroautophagy. Recently it was pro...
journal_title:Autophagy
pub_type: 杂志文章
doi:10.4161/auto.6059
更新日期:2008-05-01 00:00:00
abstract::ISG15 (ISG15 ubiquitin-like modifier), a ubiquitin-like protein, is one of the major type I IFN (interferon) effector systems. ISG15 can be conjugated to target proteins (ISGylation) via the stepwise action of E1, E2, and E3 enzymes. Conjugated ISG15 can be removed (deISGylated) from target proteins by USP18 (ubiquiti...
journal_title:Autophagy
pub_type: 杂志文章
doi:10.1080/15548627.2015.1023982
更新日期:2015-04-03 00:00:00
abstract::Autophagy is a critical cellular homeostatic process that controls the turnover of damaged organelles and proteins. Impaired autophagic activity is involved in a number of diseases, including idiopathic pulmonary fibrosis suggesting that altered autophagy may contribute to fibrogenesis. However, the specific role of a...
journal_title:Autophagy
pub_type: 杂志文章
doi:10.1080/15548627.2015.1034409
更新日期:2015-04-03 00:00:00
abstract::In a recent paper we addressed the mechanism by which defective autophagy contributes to TARDBP/TDP-43-mediated neurodegenerative disorders. We demonstrated that TARDBP regulates MTORC1-TFEB signaling by targeting RPTOR/raptor, a key component and an adaptor protein of MTORC1. Loss of TARDBP decreased the mRNA stabili...
journal_title:Autophagy
pub_type: 杂志文章
doi:10.1080/15548627.2016.1151596
更新日期:2016-01-01 00:00:00
abstract::A wide variety of genetic, pharmacological and nutrient manipulations that extend lifespan in model organisms do so in a manner dependent upon increased autophagic flux. However, our recent findings suggest that when mitochondrial membrane integrity is compromised, macroautophagy/autophagy can be detrimental. In C. el...
journal_title:Autophagy
pub_type: 杂志文章
doi:10.1080/15548627.2019.1644077
更新日期:2019-10-01 00:00:00
abstract::In the fungal pathogen Fusarium oxysporum, vegetative hyphal fusion triggers nuclear mitotic division in the invading hypha followed by migration of a nucleus into the receptor hypha and degradation of the resident nucleus. Here we examined the role of autophagy in fusion-induced nuclear degradation. A search of the F...
journal_title:Autophagy
pub_type: 杂志文章
doi:10.4161/15548627.2014.994413
更新日期:2015-01-01 00:00:00
abstract::The bioactive sphingolipid metabolite sphingosine-1-phosphate (S1P) and the enzyme that produces it, SPHK1 (sphingosine kinase 1), regulate many processes important for the etiology of cancer. It has been suggested that SPHK1 levels are regulated by the tumor suppressor protein TP53, a key regulator of cell cycle arre...
journal_title:Autophagy
pub_type: 杂志文章
doi:10.1080/15548627.2018.1429875
更新日期:2018-01-01 00:00:00
abstract::Loss-of-function mutations in PARK2/PARKIN and PINK1 cause early-onset autosomal recessive Parkinson disease (PD). The cytosolic E3 ubiquitin-protein ligase PARK2 cooperates with the mitochondrial kinase PINK1 to maintain mitochondrial quality. A loss of mitochondrial transmembrane potential (ΔΨ) leads to the PINK1-de...
journal_title:Autophagy
pub_type: 杂志文章
doi:10.4161/auto.25884
更新日期:2013-11-01 00:00:00
abstract::To maintain proper cellular homeostasis, the magnitude of autophagy activity has to be finely tuned in response to environmental changes. Many aspects of autophagy regulation have been extensively studied: pathways integrating signals through the master regulators TORC1 and PKA lead to multiple post-translational modi...
journal_title:Autophagy
pub_type: 杂志文章
doi:10.1080/15548627.2015.1018503
更新日期:2015-04-03 00:00:00
abstract::Formation of metastases, also known as cancer dissemination, is an important stage of breast cancer (BrCa) development. KISS1 expression is associated with inhibition of metastases development. Recently we have demonstrated that BrCa metastases to the brain exhibit low levels of KISS1 expression at both mRNA and prote...
journal_title:Autophagy
pub_type: 杂志文章
doi:10.1080/15548627.2017.1360466
更新日期:2017-01-01 00:00:00
abstract::Autophagy acts as an intrinsic defense system against intracellular bacterial survival. Recently, multiple cellular pathways that target intracellular bacterial pathogens to autophagy have been described. These include the Atg5/LC3 pathway, which targets Shigella, the ubiquitin (Ub)-NDP52-LC3 pathway, which targets Gr...
journal_title:Autophagy
pub_type: 杂志文章,评审
doi:10.4161/auto.7.3.14581
更新日期:2011-03-01 00:00:00
abstract::Adaptive immunity, which plays an important role in the development of atherosclerosis, is mediated by major histocompatibility complex (MHC)-dependent antigen presentation. In atherosclerotic lesions, macrophages constitute an important class of antigen-presenting cells that activate adaptive immune responses to oxid...
journal_title:Autophagy
pub_type: 杂志文章
doi:10.1080/15548627.2015.1037061
更新日期:2015-01-01 00:00:00
abstract::Based on a functional categorization, proteins may be grouped into three types and sorted to either the proteasome or the macroautophagy pathway for degradation. The two pathways are mechanistically connected but their capacity seems different. Macroautophagy can degrade all forms of misfolded proteins whereas proteas...
journal_title:Autophagy
pub_type: 杂志文章,评审
doi:10.4161/auto.5190
更新日期:2008-02-01 00:00:00