Abstract:
:The macroautophagy/autophagy-lysosome axis enables the clearance and degradation of cytoplasmic components including protein aggregates, damaged organelles and invading pathogens. Protein aggregation and lysosomal system dysfunction in the brain are common features of several late-onset neurological disorders including Alzheimer disease. Spatial overlap between depletion of the endosomal-sorting complex retromer and MAPT/tau aggregation in the brain have been previously reported. However, whether retromer dysfunction plays a direct role in mediating MAPT aggregation remains unclear. Here, we demonstrate that the autophagy-lysosome axis is the primary mode for the clearance of aggregated species of MAPT using both chemical and genetic approaches in cell models of amyloid MAPT aggregation. We show that depletion of the central retromer component VPS35 causes a block in the resolution of autophagy. We establish that this defect underlies marked accumulation of cytoplasmic MAPT aggregates upon VPS35 depletion, and that VPS35 overexpression has the opposite effect. This work illustrates how retromer complex integrity regulates the autophagy-lysosome axis to suppress MAPT aggregation and spread.
journal_name
Autophagyjournal_title
Autophagyauthors
Carosi JM,Hein LK,van den Hurk M,Adams R,Milky B,Singh S,Bardy C,Denton D,Kumar S,Sargeant TJdoi
10.1080/15548627.2020.1821545subject
Has Abstractpub_date
2020-09-22 00:00:00pages
1-21eissn
1554-8627issn
1554-8635pub_type
杂志文章相关文献
Autophagy文献大全abstract::The autophagy-lysosome system is essential for muscle cell homeostasis and its dysfunction has been linked to muscle disorders that are typically distinguished by massive autophagic buildup. Among them, glycogen storage disease type II (GSDII) is characterized by the presence of large glycogen-filled lysosomes in the ...
journal_title:Autophagy
pub_type: 杂志文章
doi:10.4161/auto.21691
更新日期:2012-11-01 00:00:00
abstract::UVRAG is a promoter of the autophagy pathway, and its deficiency may fuel the development of cancers. Intriguingly, our recent study has demonstrated that this protein also mediates the repair of damaged DNA and patrols centrosome stability, mechanisms that commonly prevent cancer progression, in a manner independent ...
journal_title:Autophagy
pub_type: 杂志文章
doi:10.4161/auto.21035
更新日期:2012-09-01 00:00:00
abstract::Recent studies have suggested that autophagy is involved in a neural death pathway following cerebral ischemia. In vivo detection of autophagy could be important for evaluating ischemic neural cell damage for human stroke patients. Using novel green fluorescent protein (GFP)-fused microtubule-associated protein 1 ligh...
journal_title:Autophagy
pub_type: 杂志文章
doi:10.4161/auto.6.8.13427
更新日期:2010-11-01 00:00:00
abstract::Induced pluripotent stem cells (iPSCs) have fewer and immature mitochondria than somatic cells and mainly rely on glycolysis for energy source. During somatic cell reprogramming, somatic mitochondria and other organelles get remodeled. However, events of organelle remodeling and interaction during somatic cell reprogr...
journal_title:Autophagy
pub_type: 杂志文章
doi:10.1080/15548627.2017.1338545
更新日期:2017-09-02 00:00:00
abstract::Coxsackievirus B3 (CVB3) has previously been shown to utilize autophagy in an advantageous manner during the course of infection of the host cell. However, few studies have determined whether stem cells induce autophagy in a similar fashion, and whether virus-induced autophagy occurs following infection of stem cells....
journal_title:Autophagy
pub_type: 杂志文章
doi:10.4161/auto.19781
更新日期:2012-06-01 00:00:00
abstract::Heme is an essential molecule expressed in many tissues where it plays key roles as the prosthetic group of several proteins involved in vital physiological and metabolic processes such as gas and electron transport. Structurally, heme is a tetrapyrrole ring containing an atom of iron (Fe) in its center. When released...
journal_title:Autophagy
pub_type: 杂志文章
doi:10.1080/15548627.2016.1271515
更新日期:2017-03-04 00:00:00
abstract::Intervertebral disc degeneration (IDD) is the primary pathological mechanism that underlies low back pain. Overloading-induced cell death, especially endogenous stem cell death, is the leading factor that undermines intrinsic repair and aggravates IDD. Previous research has separately studied the effect of oxygen conc...
journal_title:Autophagy
pub_type: 杂志文章
doi:10.1080/15548627.2021.1872227
更新日期:2021-01-18 00:00:00
abstract::Apoptosis (programmed cell death type I) and autophagy (type II) are crucial mechanisms regulating cell death and homeostasis. The Bcl-2 proto-oncogene is overexpressed in 50-70% of breast cancers, potentially leading to resistance to chemotherapy, radiation and hormone therapy-induced apoptosis. Here, we investigated...
journal_title:Autophagy
pub_type: 杂志文章
doi:10.4161/auto.6083
更新日期:2008-07-01 00:00:00
abstract::Nanotechnology is the control and manipulation of materials in the size range of 1-100 nm. Due to increasing research into the potential beneficial applications of nanotechnology, there is an urgent need for the study of possible health risks. Several researchers, including those in our laboratory, have demonstrated e...
journal_title:Autophagy
pub_type: 杂志文章
doi:10.4161/auto.7142
更新日期:2008-11-01 00:00:00
abstract::Mutations in the ER-associated VAPB/ALS8 protein cause amyotrophic lateral sclerosis and spinal muscular atrophy. Previous studies have argued that ER stress may underlie the demise of neurons. We find that loss of VAP proteins (VAPs) leads to an accumulation of aberrant lysosomes and impairs lysosomal degradation. VA...
journal_title:Autophagy
pub_type: 杂志文章
doi:10.1080/15548627.2019.1580103
更新日期:2019-07-01 00:00:00
abstract::We have reported in a variety of mammalian cells the reversible formation of a filamentous actin (F-actin)-enriched aggresome generated by the actin toxin jasplakinolide (Lázaro-Diéguez et al., J Cell Sci 2008; 121:1415-25). Notably, this F-actin aggresome (FAG) resembles in many aspects the pathological Hirano body, ...
journal_title:Autophagy
pub_type: 杂志文章
doi:10.4161/auto.6345
更新日期:2008-07-01 00:00:00
abstract::Ferroptosis is a form of regulated cell death caused by iron accumulation and oxidative injury. BECN1 is a key regulator of macroautophagy/autophagy, a catabolic process of degradation induced by starvation or other stressors. Our recent findings reveal a novel alternative mechanism by which BECN1 can promote ferropto...
journal_title:Autophagy
pub_type: 评论,杂志文章
doi:10.1080/15548627.2018.1513758
更新日期:2018-01-01 00:00:00
abstract::The European autophagy consortium Driving next-generation autophagy researchers towards translation (DRIVE) held its kick-off meeting in Groningen on the 14th and 15th of June 2018. This Marie Skłodowska-Curie Early Training Network was approved under the European Union's Horizon 2020 Research and Innovation Program a...
journal_title:Autophagy
pub_type: 杂志文章
doi:10.1080/15548627.2018.1515532
更新日期:2019-02-01 00:00:00
abstract::Macroautophagy is an intracellular catabolic process involved in the formation of multiple membrane structures ranging from phagophores to autophagosomes and autolysosomes. Dysfunction of macroautophagy is implicated in both physiological and pathological conditions. To date, 38 autophagy-related (ATG) genes have been...
journal_title:Autophagy
pub_type: 杂志文章,评审
doi:10.4161/15548627.2014.984267
更新日期:2015-01-01 00:00:00
abstract::Autophagy plays critical roles in plant responses to stress. In contrast to the wealth of information concerning the core process of plant autophagosome assembly, our understanding of the regulation of autophagy is limited. In this study, we demonstrated that transcription factor HsfA1a played a critical role in tomat...
journal_title:Autophagy
pub_type: 杂志文章
doi:10.1080/15548627.2015.1098798
更新日期:2015-11-02 00:00:00
abstract::Lafora disease (LD) is an inherited and fatal form of neurodegenerative disorder characterized by the presence of an abnormal form of glycogen inclusions, called Lafora bodies, in neurons and other tissues. While Lafora bodies have been thought to underlie the neuropathology in LD, the specific process by which these ...
journal_title:Autophagy
pub_type: 杂志文章,评审
doi:10.4161/auto.8.2.19010
更新日期:2012-02-01 00:00:00
abstract::Several recent reports have demonstrated that autophagy is induced in response to hypoxia in cultured cells. However, the mechanism and consequence of hypoxia-induced autophagy remains unclear as there is no consensus between these studies. In our recent report we show that, in human cancer cells, hypoxia cooperates w...
journal_title:Autophagy
pub_type: 杂志文章
doi:10.4161/auto.5.7.9821
更新日期:2009-10-01 00:00:00
abstract::Oxidative stress (OS) stimulates autophagy in different cellular systems, but it remains controversial if this rule can be generalized. We have analyzed the effect of chronic OS induced by the parkinsonian toxin paraquat (PQ) on autophagy in astrocytoma cells and primary astrocytes, which represent the first cellular ...
journal_title:Autophagy
pub_type: 杂志文章
doi:10.1080/15548627.2015.1058683
更新日期:2015-01-01 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::Accumulating evidence has demonstrated that macroautophagy/autophagy plays an essential role in self-renewal and differentiation in embryonic hematopoiesis. Here, according to the RNA sequencing data sets of 5 population cells related to hematopoietic stem cell (HSC) formation during mouse embryogenesis (endothelial c...
journal_title:Autophagy
pub_type: 杂志文章
doi:10.1080/15548627.2016.1278093
更新日期:2017-04-03 00:00:00
abstract::Autophagy research continues to expand exponentially. Clearly autophagy and metabolism are intimately connected; however, the rapid expansion of research into this topic inevitably brings the risk that important basic knowledge of metabolism will be overlooked when considering experimental data. Unfortunately, unaware...
journal_title:Autophagy
pub_type: 杂志文章
doi:10.4161/auto.5.1.7207
更新日期:2009-01-01 00:00:00
abstract::Neuroepithelial cells undergoing differentiation efficiently remodel their cytoskeleton and shape in an energy-consuming process. The capacity of autophagy to recycle cellular components and provide energy could fulfill these requirements, thus supporting differentiation. However, little is known regarding the role of...
journal_title:Autophagy
pub_type: 杂志文章
doi:10.4161/auto.8.2.18535
更新日期:2012-02-01 00:00:00
abstract::The aging process drives the progressive deterioration of an organism and is thus subject to a complex interplay of regulatory and executing mechanisms. Our understanding of this process eventually aims at the delay and/or prevention of age-related pathologies, among them the age-dependent decrease in cognitive perfor...
journal_title:Autophagy
pub_type: 杂志文章
doi:10.4161/auto.26918
更新日期:2014-01-01 00:00:00
abstract::Reactive oxygen species (ROS) that accumulate under oxidative pressure cause severe damage to cellular components, and induce various cellular responses, including apoptosis, programmed necrosis and autophagy, depending on the cellular setting. Various studies have described ROS-induced autophagy, but only a few direc...
journal_title:Autophagy
pub_type: 杂志文章
doi:10.4161/auto.19288
更新日期:2012-03-01 00:00:00
abstract::Upon completion of cytokinesis, the midbody ring is transported asymmetrically into one of the two daughter cells where it becomes a midbody ring derivative that is degraded by autophagy. In this study we showed that the ubiquitin-binding autophagy receptor SQSTM1/p62 and the interacting adaptor protein WDFY3/ALFY for...
journal_title:Autophagy
pub_type: 杂志文章
doi:10.4161/auto.26085
更新日期:2013-12-01 00:00:00
abstract::Neuroblastoma is the most common extracranial solid tumor in childhood. Despite intense multimodal therapy and many improvements through basic scientific and clinical research, the successful response of advanced-stage patients to chemotherapy remains poor. Autophagy is a cytoprotective mechanism that may help advance...
journal_title:Autophagy
pub_type: 杂志文章
doi:10.4161/auto.26450
更新日期:2013-12-01 00:00:00
abstract::Dysfunction of macroautophagy/autophagy has been postulated as a major cellular toxicological response to nanomaterials. It has been reported that excessive autophagy activation, induced by silica nanoparticles (SiNPs), contributes to autophagy dysfunction, whereas little is known how SiNPs trigger autophagy activatio...
journal_title:Autophagy
pub_type: 杂志文章
doi:10.1080/15548627.2020.1763019
更新日期:2020-05-23 00:00:00
abstract::Numerous cardiomyocytes were found to show autophagic vacuolar degeneration in the UM-X7.1 hamster model of human dilated cardiomyopathy, and autophagy-related proteins--i.e., ubiquitin, cathepsin D and Rab7--were upregulated in those hearts. Importantly, Evans blue-positive cardiomyocytes with leaky plasma membranes ...
journal_title:Autophagy
pub_type: 杂志文章,评审
doi:10.4161/auto.2608
更新日期:2006-07-01 00:00:00
abstract::Recent evidence suggests that autophagy may favor fibrosis through enhanced differentiation of fibroblasts in myofibroblasts. Here, we sought to characterize the mediators and signaling pathways implicated in autophagy-induced myofibroblast differentiation. Fibroblasts, serum starved for up to 4 d, showed increased LC...
journal_title:Autophagy
pub_type: 杂志文章
doi:10.4161/15548627.2014.981786
更新日期:2014-01-01 00:00:00
abstract::Prion protein modulates many cellular functions including the secretion of trophic factors by astrocytes. Some of these factors are found in exosomes, which are formed within multivesicular bodies (MVBs) and secreted into the extracellular space to modulate cell-cell communication. The mechanisms underlying exosome bi...
journal_title:Autophagy
pub_type: 杂志文章
doi:10.1080/15548627.2016.1226735
更新日期:2016-11-01 00:00:00