Lysosomal Biology and Function: Modern View of Cellular Debris Bin

Trivedi, Purvi; Bartlett, Jordan; Pulinilkunnil, Thomas

doi:10.3390/cells9051131

Cited by 201 publications

(165 citation statements)

References 258 publications

(404 reference statements)

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“…Lysosomal exocytosis is a Ca + regulated process, in which lysosomes move outward to the cellular periphery and fuse with the plasma membrane, emptying their luminal protons and proteases [ 59 ]. By virtue of the dynamic feature of lysosomal exocytosis, excessive protons generated by aerobic glycolysis can continuously follow the route of lysosomes and escape from cancer cells.…”

Section: Ph Gradient Reversal Regulated By Lysosomal Functionsmentioning

confidence: 99%

Lysosome as a Central Hub for Rewiring PH Homeostasis in Tumors

Chen

Jäättelä

Liu

2020

Cancers

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Cancer cells generate large quantities of cytoplasmic protons as byproducts of aberrantly activated aerobic glycolysis and lactate fermentation. To avoid potentially detrimental acidification of the intracellular milieu, cancer cells activate multiple acid-removal pathways that promote cytosolic alkalization and extracellular acidification. Accumulating evidence suggests that in addition to the well-characterized ion pumps and exchangers in the plasma membrane, cancer cell lysosomes are also reprogrammed for this purpose. On the one hand, the increased expression and activity of the vacuolar-type H+−ATPase (V-ATPase) on the lysosomal limiting membrane combined with the larger volume of the lysosomal compartment increases the lysosomal proton storage capacity substantially. On the other hand, enhanced lysosome exocytosis enables the efficient release of lysosomal protons to the extracellular space. Together, these two steps dynamically drive proton flow from the cytosol to extracellular space. In this perspective, we provide mechanistic insight into how lysosomes contribute to the rewiring of pH homeostasis in cancer cells.

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Section: Ph Gradient Reversal Regulated By Lysosomal Functionsmentioning

confidence: 99%

Lysosome as a Central Hub for Rewiring PH Homeostasis in Tumors

Chen

Jäättelä

Liu

2020

Cancers

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“…Therefore, when an LE/MVB fuses with an autophagosome, it may for a period have a double membrane, prior to fusing with a lysosome to form an autolysosome (Figure 1) [33,35]. Further sorting of cargo occurs in the lysosome/lysosomal fusion structures (Figure 1); proteins not for degradation are released as vesicles via clathrin pathways [36,37] or by exocytosis [33].…”

Section: Cell Trafficking and Secretory Pathways As Ultrastructural ‘mentioning

confidence: 99%

Ultrastructure of cell trafficking pathways and coronavirus: how to recognise the wolf amongst the sheep

Neil

Moran

Horsfield

et al. 2020

The Journal of Pathology

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The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic has resulted in an urgent need to understand the pathophysiology of SARS-CoV2 infection, to assist in the identification of treatment strategies. Viral tissue tropism is an active area of investigation, one approach to which is identification of virus within tissues by electron microscopy of post-mortem and surgical specimens. Most diagnostic histopathologists have limited understanding of the ultrastructural features of normal cell trafficking pathways, which can resemble intra-and extracellular coronavirus; in addition, viral replication pathways make use of these trafficking pathways. Herein, we review these pathways and their ultrastructural appearances, with emphasis on structures which may be confused with coronavirus. In particular, we draw attention to the fact that, when using routine fixation and processing, the typical 'crown' that characterises a coronavirus is not readily identified on intracellular virions, which are located in membrane-bound vacuoles. In addition, the viral nucleocapsid is seen as black dots within the virion and is more discriminatory in differentiating virions from other cellular structures. The identification of the viral replication organelle, a collection of membranous structures (convoluted membranes) seen at a relatively low scanning power, may help to draw attention to infected cells, which can be sparse.

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“…The substance (amino acid, etc.) is eventually degraded, which is then either recycled or removed into extracellular space [48]. Subsequently, the lysosomal fraction of the autolysosomes is recovered to produce new lysosomes [49].…”

Section: Molecular Mechanism Of the Fusion Of Aggresome And Lysosomementioning

confidence: 99%

“…Subsequently, the lysosomal fraction of the autolysosomes is recovered to produce new lysosomes [49]. Rab7A (Ypt7 in yeast), mature autophagosome, HOPS (homologous protein fusion and classification complex) and SNARE receptor (SNAP (soluble adhesion protein NSF)) (NSF, fusion-sensitive) labeled (ethyl-maleimide) proteins are essential for the fusion of autophagosomes and lysosomes [48]. The SNAREs increases the permeability of the membrane, forming the membrane opening and fusing the content of two adjacent organelles [50].…”

Section: Molecular Mechanism Of the Fusion Of Aggresome And Lysosomementioning

confidence: 99%

Emerging Potential Role of Autophagy to Modulate Aggresome Formation: Insights Molecular Treatment of Alzheimer’s Disease

Rahman¹,

Rahman²,

Mamun-Or-Rashid³

et al. 2021

Preprint

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Alzheimer’s disease (AD) is one of the most prevailing neurodegenerative diseases in the world, which is characterized by memory dysfunction and the formation of tau and amyloid β (Aβ) aggregate in multiple brain regions, including the hippocampus and cortex. The formation of senile plaques involving tau hyperphosphorylation, fibrillar Aβ, and neurofibrillary tangles (NFTs) are used as pathological markers of AD, and eventually produces aggregation or misfolded protein. Importantly, it has been found that failure to degrade these aggregate-prone proteins leads to pathological consequences, such as synaptic impairment, cytotoxicity, neuronal atrophy, and memory deficits associated with AD. Recently, increasing evidences have been suggested that autophagy pathway plays a role as a central cellular protection system to prevent the toxicity induced by aggregate or misfolded proteins. Moreover, it has also been related that AD-related protein aggresomes could be selectively degraded by autophagosome and lysosomal fusion through autophagy pathway which is known as aggrephagy. Therefore, the regulation of autophagy might be served as a useful approach to modulate the formation of aggresome associated in AD. This review focuses on the recent improvements in the application of natural compounds and small molecules as a potential therapeutic approach for AD prevention and treatment via aggrephagy.

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Lysosomal Biology and Function: Modern View of Cellular Debris Bin

Cited by 201 publications

References 258 publications

Lysosome as a Central Hub for Rewiring PH Homeostasis in Tumors

Lysosome as a Central Hub for Rewiring PH Homeostasis in Tumors

Ultrastructure of cell trafficking pathways and coronavirus: how to recognise the wolf amongst the sheep

Emerging Potential Role of Autophagy to Modulate Aggresome Formation: Insights Molecular Treatment of Alzheimer’s Disease

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