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Oncotarget Mar 2017
Topics: Animals; Autophagy; Cell Biology; Humans; Lysosomes
PubMed: 28423641
DOI: 10.18632/oncotarget.15951 -
Cell Apr 2020In addition to their well-defined recycling function, lysosomes act as metabolic signaling hubs that adjust cellular metabolism according to the availability of...
In addition to their well-defined recycling function, lysosomes act as metabolic signaling hubs that adjust cellular metabolism according to the availability of nutrients and growth factors by regulating metabolic kinases and transcription factors on their surface. Moreover, lysosomal hydrolases and ions released to cytosol or extracellular space have recently emerged as important regulators of various cellular processes from cell death to cell division. To view this SnapShot, open or download the PDF.
Topics: Autophagy; Cytosol; Extracellular Space; Humans; Hydrolases; Lysosomes; Phosphotransferases; Signal Transduction; Transcription Factors
PubMed: 32359442
DOI: 10.1016/j.cell.2020.03.043 -
Nature Reviews. Molecular Cell Biology Jun 2021
Topics: Biological Transport; Lysosomes
PubMed: 33911233
DOI: 10.1038/s41580-021-00376-4 -
Trends in Biochemical Sciences Nov 2020Lysosomes transcend the role of degradation stations, acting as key nodes for interorganelle crosstalk and signal transduction. Lysosomes communicate with the nucleus... (Review)
Review
Lysosomes transcend the role of degradation stations, acting as key nodes for interorganelle crosstalk and signal transduction. Lysosomes communicate with the nucleus through physical proximity and functional interaction. In response to external and internal stimuli, lysosomes actively adjust their distribution between peripheral and perinuclear regions and modulate lysosome-nucleus signaling pathways; in turn, the nucleus fine-tunes lysosomal biogenesis and functions through transcriptional controls. Changes in coordination between these two essential organelles are associated with metabolic disorders, neurodegenerative diseases, and aging. In this review, we address recent advances in lysosome-nucleus communication by multi-tiered regulatory mechanisms and discuss how these regulations couple metabolic inputs with organellar motility, cellular signaling, and transcriptional network.
Topics: Animals; Cell Nucleus; Gene Regulatory Networks; Humans; Lysosomes; Signal Transduction
PubMed: 32624271
DOI: 10.1016/j.tibs.2020.06.004 -
Annual Review of Pharmacology and... Jan 2023Lysosomes play fundamental roles in material digestion, cellular clearance, recycling, exocytosis, wound repair, Ca signaling, nutrient signaling, and gene expression... (Review)
Review
Lysosomes play fundamental roles in material digestion, cellular clearance, recycling, exocytosis, wound repair, Ca signaling, nutrient signaling, and gene expression regulation. The organelle also serves as a hub for important signaling networks involving the mTOR and AKT kinases. Electrophysiological recording and molecular and structural studies in the past decade have uncovered several unique lysosomal ion channels and transporters, including TPCs, TMEM175, TRPMLs, CLN7, and CLC-7. They underlie the organelle's permeability to major ions, including K, Na, H, Ca, and Cl. The channels are regulated by numerous cellular factors, ranging from H in the lumen and voltage across the lysosomal membrane to ATP in the cytosol to growth factors outside the cell. Genetic variations in the channel/transporter genes are associated with diseases that include lysosomal storage diseases and neurodegenerative diseases. Recent studies with human genetics and channel activators suggest that lysosomal channels may be attractive targets for the development of therapeutics for the prevention of and intervention in human diseases.
Topics: Humans; Ion Channels; Signal Transduction; Lysosomes; Neurodegenerative Diseases
PubMed: 36151054
DOI: 10.1146/annurev-pharmtox-051921-013755 -
Methods (San Diego, Calif.) Jan 2017The use of multispectral imaging flow cytometry has been gaining popularity due to its quantitative power, high throughput capabilities, multiplexing potential and its... (Review)
Review
The use of multispectral imaging flow cytometry has been gaining popularity due to its quantitative power, high throughput capabilities, multiplexing potential and its ability to acquire images of every cell. Autophagy is a process in which dysfunctional organelles and cellular components that accumulate during growth and differentiation are degraded via the lysosome and recycled. During autophagy, cytoplasmic LC3 is processed and recruited to the autophagosomal membranes; the autophagosome then fuses with the lysosome to form the autolysosome. Therefore, cells undergoing autophagy can be identified by visualizing fluorescently labeled LC3 puncta and/or the co-localization of fluorescently labeled LC3 and lysosomal markers. Multispectral imaging flow cytometry is able to collect imagery of large numbers of cells and assess autophagy in an objective, quantitative, and statistically robust manner. This review will examine the four predominant methods that have been used to measure autophagy via multispectral imaging flow cytometry.
Topics: Antibodies; Autophagosomes; Autophagy; Carbocyanines; Chloroquine; Flow Cytometry; Fluorescent Dyes; Green Fluorescent Proteins; Humans; Image Cytometry; Jurkat Cells; Lysosomal Membrane Proteins; Lysosomes; Microtubule-Associated Proteins; Staining and Labeling
PubMed: 27263026
DOI: 10.1016/j.ymeth.2016.05.022 -
Biomolecules Jun 2021Lysosomal storage disorders (LSDs) are a group of 60 rare inherited diseases characterized by a heterogeneous spectrum of clinical symptoms, ranging from severe...
Lysosomal storage disorders (LSDs) are a group of 60 rare inherited diseases characterized by a heterogeneous spectrum of clinical symptoms, ranging from severe intellectual disabilities, cardiac abnormalities, visceromegaly, and bone deformities to slowly progressive muscle weakness, respiratory insufficiency, eye defects (corneal clouding and retinal degeneration), and skin alterations [...].
Topics: Humans; Lysosomal Storage Diseases; Lysosomes
PubMed: 34208892
DOI: 10.3390/biom11070964 -
CNS Drugs Jul 2019Disturbed proteostasis as reflected by a massive accumulation of misfolded protein aggregates is a central feature in Alzheimer's disease. Proteostatic disturbances may... (Review)
Review
Disturbed proteostasis as reflected by a massive accumulation of misfolded protein aggregates is a central feature in Alzheimer's disease. Proteostatic disturbances may be caused by a shift in protein production and clearance. Whereas rare genetic causes of the disease affect the production side, sporadic cases appear to be directed by dysfunction in protein clearance. This review focusses on the involvement of lysosome-mediated clearance. Autophagy is a degradational system where intracellular components are degraded by lysosomal organelles. In addition, "outside-to-inside" trafficking through the endosomes converges with the autolysosomal pathway, thereby bringing together intracellular and extracellular components. Recent findings demonstrate that disturbance in the endo- and autolysosomal pathway induces "inside-to-outside" communication via induction of unconventional secretion, which may bear relevance to the spreading of disease pathology through the brain. The involvement of these pathways in the pathogenesis of the disease is discussed with an outlook to the opportunities it provides for diagnostics as well as therapeutic interventions.
Topics: Alzheimer Disease; Animals; Autophagy; Brain; Endosomes; Humans; Lysosomes
PubMed: 31165364
DOI: 10.1007/s40263-019-00643-1 -
Current Medicinal Chemistry 2018Mitochondrial diseases may result from mutations in the maternally-inherited mitochondrial DNA (mtDNA) or from mutations in nuclear genes encoding mitochondrial... (Review)
Review
Mitochondrial diseases may result from mutations in the maternally-inherited mitochondrial DNA (mtDNA) or from mutations in nuclear genes encoding mitochondrial proteins. Their bi-genomic nature makes mitochondrial diseases a very heterogeneous group of disorders that can present at any age and can affect any type of tissue. The autophagic-lysosomal degradation pathway plays an important role in clearing dysfunctional and redundant mitochondria through a specific quality control mechanism termed mitophagy. Mitochondria could be targeted for autophagic degradation for a variety of reasons including basal turnover for recycling, starvation induced degradation, and degradation due to damage. While the core autophagic machinery is highly conserved and common to most pathways, the signaling pathways leading to the selective degradation of damaged mitochondria are still not completely understood. Type 1 mitophagy due to nutrient starvation is dependent on PI3K (phosphoinositide 3-kinase) for autophagosome formation but independent of mitophagy proteins, PINK1 (PTEN-induced putative kinase 1) and Parkin. Whereas type 2 mitophagy that occurs due to damage is dependent on PINK1 and Parkin but does not require PI3K. Autophagy and mitophagy play an important role in human disease and hence could serve as therapeutic targets for the treatment of mitochondrial as well as neurodegenerative disorders. Therefore, we reviewed drugs that are known modulators of autophagy (AICAR and metformin) and may affect this by activating the AMP-activated protein kinase signaling pathways. Furthermore, we reviewed the data available on supplements, such as Coenzyme Q and the quinone idebenone, that we assert rescue increased mitophagy in mitochondrial disease by benefiting mitochondrial function.
Topics: Animals; Autophagy; Humans; Lysosomes; Mitochondria; Mitochondrial Diseases; Mitophagy
PubMed: 28618992
DOI: 10.2174/0929867324666170616101741 -
Methods (San Diego, Calif.) Mar 2015Autophagy is a bulk degradation system that is induced under stress conditions such as nutrient deprivation. Selective autophagy, including xenophagy and mitophagy, is...
Autophagy is a bulk degradation system that is induced under stress conditions such as nutrient deprivation. Selective autophagy, including xenophagy and mitophagy, is believed to play important roles in the development of several diseases. Consequently, selective autophagy represents a potential therapeutic target. Recent work showed that the lysosome, a membrane-bound acidic organelle, is selectively sequestered by autophagy when its membrane is injured; this phenomenon is called "lysophagy". Lysosomes can be injured by diverse causes, including amyloid proteins and mineral crystals such as silica and monosodium urate, which would trigger neurodegeneration and other diseases. In this section, we provide an overview of methods for monitoring lysophagy in mammalian cultured cells. These methods can be used to evaluate the involvement of molecules of interest in selective autophagy, and in screens aimed at identifying novel proteins engaged in selective autophagy.
Topics: Animals; Autophagy; Humans; Lysosomes; Mitochondria; Molecular Biology
PubMed: 25542097
DOI: 10.1016/j.ymeth.2014.12.014