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Cells Feb 2023Autophagy-the lysosomal degradation of cytoplasm-plays a central role in cellular homeostasis and protects cells from potentially harmful agents that may accumulate in... (Review)
Review
Autophagy-the lysosomal degradation of cytoplasm-plays a central role in cellular homeostasis and protects cells from potentially harmful agents that may accumulate in the cytoplasm, including pathogens, protein aggregates, and dysfunctional organelles. This process is initiated by the formation of a phagophore membrane, which wraps around a portion of cytoplasm or cargo and closes to form a double-membrane autophagosome. Upon the fusion of the autophagosome with a lysosome, the sequestered material is degraded by lysosomal hydrolases in the resulting autolysosome. Several alternative membrane sources of autophagosomes have been proposed, including the plasma membrane, endosomes, mitochondria, endoplasmic reticulum, lipid droplets, hybrid organelles, and de novo synthesis. Here, we review recent progress in our understanding of how the autophagosome is formed and highlight the proposed role of vesicles that contain the lipid scramblase ATG9 as potential seeds for phagophore biogenesis. We also discuss how the phagophore is sealed by the action of the endosomal sorting complex required for transport (ESCRT) proteins.
Topics: Autophagosomes; Macroautophagy; Autophagy; Endosomes; Cell Membrane
PubMed: 36831335
DOI: 10.3390/cells12040668 -
Autophagy Jan 2023Macroautophagy/autophagy is a cellular and energy homeostatic mechanism that contributes to maintain the number of primordial follicles, germ cell survival, and...
Macroautophagy/autophagy is a cellular and energy homeostatic mechanism that contributes to maintain the number of primordial follicles, germ cell survival, and anti-ovarian aging. However, it remains unknown whether autophagy in granulosa cells affects oocyte maturation. Here, we show a clear tendency of reduced autophagy level in human granulosa cells from women of advanced maternal age, implying a potential negative correlation between autophagy levels and oocyte quality. We therefore established a co-culture system and show that either pharmacological inhibition or genetic ablation of autophagy in granulosa cells negatively affect oocyte quality and fertilization ability. Moreover, our metabolomics analysis indicates that the adverse impact of autophagy impairment on oocyte quality is mediated by downregulated citrate levels, while exogenous supplementation of citrate can significantly restore the oocyte maturation. Mechanistically, we found that ACLY (ATP citrate lyase), which is a crucial enzyme catalyzing the cleavage of citrate, was preferentially associated with K63-linked ubiquitin chains and recognized by the autophagy receptor protein SQSTM1/p62 for selective autophagic degradation. In human follicles, the autophagy level in granulosa cells was downregulated with maternal aging, accompanied by decreased citrate in the follicular fluid, implying a potential correlation between citrate metabolism and oocyte quality. We also show that elevated citrate levels in porcine follicular fluid promote oocyte maturation. Collectively, our data reveal that autophagy in granulosa cells is a beneficial mechanism to maintain a certain degree of citrate by selectively targeting ACLY during oocyte maturation. 3-MA: 3-methyladenine; ACLY: ATP citrate lyase; AMA: advanced maternal age; CG: cortical granule; CHX: cycloheximide; CQ: chloroquine; CS: citrate synthase; COCs: cumulus-oocyte-complexes; GCM: granulosa cell monolayer; GV: germinal vesicle; MII: metaphase II stage of meiosis; PB1: first polar body; ROS: reactive oxygen species; shRNA: small hairpin RNA; SQSTM1/p62: sequestosome 1; TCA: tricarboxylic acid; TOMM20/TOM20: translocase of outer mitochondrial membrane 20; UBA: ubiquitin-associated domain; Ub: ubiquitin; WT: wild-type.
Topics: Female; Humans; Animals; Swine; Sequestosome-1 Protein; ATP Citrate (pro-S)-Lyase; Macroautophagy; Citric Acid; Autophagy; Oocytes; Citrates; Acyltransferases; Ubiquitin; Homeostasis
PubMed: 35404187
DOI: 10.1080/15548627.2022.2063005 -
Current Biology : CB Jul 2019In 1955, the biologist and Nobel Prize laureate Christian de Duve discovered that cells possess specialized organelles filled with hydrolytic enzymes and he called these...
In 1955, the biologist and Nobel Prize laureate Christian de Duve discovered that cells possess specialized organelles filled with hydrolytic enzymes and he called these organelles lysosomes. At the same time, electron microscopy studies by Novikoff and colleagues showed that intracellular dense bodies, which later turned out to be lysosomes, contain cytoplasmic components. Together, these groundbreaking observations revealed that cells can deliver cytoplasmic components to lysosomes for degradation. The hallmark of this degradative process, which de Duve called autophagy, is the formation of double-membrane-limited vesicles. Further morphological characterization of these vesicles (autophagosomes) revealed that they mainly contain bulk cytoplasm. Although this suggested that autophagy leads to a non-selective degradation of cytoplasmic material, de Duve anticipated that a regulated and selective type of this pathway must also exist. Today we know that, under normal conditions, macroautophagy is a highly selective pathway that sequesters damaged or superfluous material from the cytoplasm through the formation of double-membrane-limited autophagosomes. Upon fusion with lysosomes, the content of autophagosomes is degraded and the resulting building blocks are released into the cytoplasm. However, in response to cytotoxic stress or starvation, cells start to produce autophagosomes that capture bulk cytoplasm non-selectively. This stress response is essential for cells to survive adverse environmental conditions, whereas the selective sequestration of cargo is important to maintain cellular homeostasis.
Topics: Autophagosomes; Autophagy; Cytosol; Lysosomes; Macroautophagy
PubMed: 31336079
DOI: 10.1016/j.cub.2019.06.014 -
Autophagy Aug 2023Macroautophagy/autophagy is a cellular degradation and recycling process that maintains the homeostasis of organisms. The protein degradation role of autophagy has been...
Macroautophagy/autophagy is a cellular degradation and recycling process that maintains the homeostasis of organisms. The protein degradation role of autophagy has been widely used to control viral infection at multiple levels. In the ongoing evolutionary arms race, viruses have developed various ways to hijack and subvert autophagy in favor of its replication. It is still unclear exactly how autophagy affects or inhibits viruses. In this study, we have found a novel host restriction factor, HNRNPA1, that could inhibit PEDV replication by degrading viral nucleocapsid (N) protein. The restriction factor activates the HNRNPA1-MARCHF8/MARCH8-CALCOCO2/NDP52-autophagosome pathway with the help of transcription factor EGR1 targeting the promoter. HNRNPA1 could also promote the expression of IFN to facilitate the host antiviral defense response for antagonizing PEDV infection through RIGI protein interaction. During viral replication, we found that PEDV can, in contrast, degrade the host antiviral proteins HNRNPA1 and others (FUBP3, HNRNPK, PTBP1, and TARDBP) through its N protein through the autophagy pathway. These results reveal the dual function of selective autophagy in PEDV N and host proteins, which could promote the ubiquitination of viral particles and host antiviral proteins and degradation both of the proteins to regulate the relationship between virus infection and host innate immunity. 3-MA: 3-methyladenine; ATG: autophagy related; Baf A1: bafilomycin A; CALCOCO2/NDP52: calcium binding and coiled-coil domain 2; ChIP: chromatin immunoprecipitation; Co-IP: co-immunoprecipitation; CQ: chloroquine; DAPI: 4',6-diamidino-2-phenylindole; GPI: glycosyl-phosphatidylinositol; hpi: hours post infection; MARCHF8/MARCH8: membrane-associated ring-CH-type finger 8; MOI: multiplicity of infection; N protein: nucleocapsid protein; PEDV: porcine epidemic diarrhea virus; siRNA: small interfering RNA; TCID: 50% tissue culture infectious doses.
Topics: Animals; Swine; Porcine epidemic diarrhea virus; Macroautophagy; Autophagy; Antiviral Agents; Nucleocapsid Proteins; Coronavirus Infections
PubMed: 36861818
DOI: 10.1080/15548627.2023.2181615 -
The Journal of Cell Biology Oct 2022A ferritin particle consists of 24 ferritin proteins (FTH1 and FTL) and stores iron ions within it. During iron deficiency, ferritin particles are transported to...
A ferritin particle consists of 24 ferritin proteins (FTH1 and FTL) and stores iron ions within it. During iron deficiency, ferritin particles are transported to lysosomes to release iron ions. Two transport pathways have been reported: macroautophagy and ESCRT-dependent endosomal microautophagy. Although the membrane dynamics of these pathways differ, both require NCOA4, which is thought to be an autophagy receptor for ferritin. However, it is unclear whether NCOA4 only acts as an autophagy receptor in ferritin degradation. Here, we found that ferritin particles form liquid-like condensates in a NCOA4-dependent manner. Homodimerization of NCOA4 and interaction between FTH1 and NCOA4 (i.e., multivalent interactions between ferritin particles and NCOA4) were required for the formation of ferritin condensates. Disruption of these interactions impaired ferritin degradation. Time-lapse imaging and three-dimensional correlative light and electron microscopy revealed that these ferritin-NCOA4 condensates were directly engulfed by autophagosomes and endosomes. In contrast, TAX1BP1 was not required for the formation of ferritin-NCOA4 condensates but was required for their incorporation into autophagosomes and endosomes. These results suggest that NCOA4 acts not only as a canonical autophagy receptor but also as a driver to form ferritin condensates to facilitate the degradation of these condensates by macroautophagy (i.e., macroferritinophagy) and endosomal microautophagy (i.e., microferritinophagy).
Topics: Autophagy; Endosomes; Ferritins; Iron; Lysosomes; Nuclear Receptor Coactivators; Phagosomes; Transcription Factors
PubMed: 36066504
DOI: 10.1083/jcb.202203102 -
Cell Death and Differentiation Jan 2020Lipophagy is a lysosomal lipolytic pathway that complements the actions of cytosolic neutral lipases. Chaperon-mediated autophagy (CMA) triggers lipid droplets (LDs)...
Lipophagy is a lysosomal lipolytic pathway that complements the actions of cytosolic neutral lipases. Chaperon-mediated autophagy (CMA) triggers lipid droplets (LDs) breakdown, to initiate lipolysis via either cytosolic lipases or macroautophagy. SIRT3, a mitochondrial NAD-dependent deacetylase, regulates the acetylation status and activity of many substrates involving in energy metabolism. However, the role of SIRT3 in regulating lipophagy is controversial. The current study showed that SIRT3 expression was decreased and the macroautophagy flux was blocked in the primary hepatocytes from high-fat diet fed mice and P/O (palmitic acid and oleic acid mixture) treated AML12 mouse hepatocytes, compared with the corresponding controls. SIRT3 overexpression promoted macroautophagy in LDs from P/O-treated hepatocytes through activating AMP-activated protein kinase (AMPK) and unc-51-like kinase 1, to boost LDs digestion. Gain of SIRT3 expression stimulated the formation of lysosome-associated membrane protein 2A (LAMP-2A)-heat shock cognate 71 kDa protein (HSC70)-perilipin-2 (PLN2) complex, to promote CMA process and reduce the stability of LDs in hepatocytes. Moreover, SIRT3 reduced the expression of stearoyl-CoA desaturase 1, to suppress lipogenesis. In addition, SIRT3 overexpression promoted LDs dispersion on detyrosinated microtubules, and directly deacetylated long-chain acyl-CoA dehydrogenase to enhance mitochondrial energetics. Taken together, SIRT3 ameliorates lipotoxicity in hepatocytes, which might be a potential target for the treatment of nonalcoholic fatty liver disease.
Topics: AMP-Activated Protein Kinase Kinases; Animals; Autophagy-Related Protein-1 Homolog; Cell Line; Chaperone-Mediated Autophagy; Diet, High-Fat; Hepatocytes; Lipid Droplets; Lipid Metabolism; Lipolysis; Macroautophagy; Male; Mice, Inbred C57BL; Microtubules; Mitochondria; Protein Kinases; Sirtuin 3; Stearoyl-CoA Desaturase
PubMed: 31160717
DOI: 10.1038/s41418-019-0356-z -
ELife Sep 2021Removal of damaged organelles via the process of selective autophagy constitutes a major form of cellular quality control. Damaged organelles are recognized by a...
Removal of damaged organelles via the process of selective autophagy constitutes a major form of cellular quality control. Damaged organelles are recognized by a dedicated surveillance machinery, leading to the assembly of an autophagosome around the damaged organelle, prior to fusion with the degradative lysosomal compartment. Lysosomes themselves are also prone to damage and are degraded through the process of lysophagy. While early steps involve recognition of ruptured lysosomal membranes by glycan-binding galectins and ubiquitylation of transmembrane lysosomal proteins, many steps in the process, and their interrelationships, remain poorly understood, including the role and identity of cargo receptors required for completion of lysophagy. Here, we employ quantitative organelle capture and proximity biotinylation proteomics of autophagy adaptors, cargo receptors, and galectins in response to acute lysosomal damage, thereby revealing the landscape of lysosome-associated proteome remodeling during lysophagy. Among the proteins dynamically recruited to damaged lysosomes were ubiquitin-binding autophagic cargo receptors. Using newly developed lysophagic flux reporters including Lyso-Keima, we demonstrate that TAX1BP1, together with its associated kinase TBK1, are both necessary and sufficient to promote lysophagic flux in both HeLa cells and induced neurons (iNeurons). While the related receptor Optineurin (OPTN) can drive damage-dependent lysophagy when overexpressed, cells lacking either OPTN or CALCOCO2 still maintain significant lysophagic flux in HeLa cells. Mechanistically, TAX1BP1-driven lysophagy requires its N-terminal SKICH domain, which binds both TBK1 and the autophagy regulatory factor RB1CC1, and requires upstream ubiquitylation events for efficient recruitment and lysophagic flux. These results identify TAX1BP1 as a central component in the lysophagy pathway and provide a proteomic resource for future studies of the lysophagy process.
Topics: Autophagy; Humans; Lysosomes; Macroautophagy; Protein Binding; Proteomics; Ubiquitin
PubMed: 34585663
DOI: 10.7554/eLife.72328 -
Autophagy Aug 2022Alphaherpesvirus infection results in severe health consequences in a wide range of hosts. USPs are the largest subfamily of deubiquitinating enzymes that play critical...
Alphaherpesvirus infection results in severe health consequences in a wide range of hosts. USPs are the largest subfamily of deubiquitinating enzymes that play critical roles in immunity and other cellular functions. To investigate the role of USPs in alphaherpesvirus replication, we assessed 13 USP inhibitors for PRV replication. Our data showed that all the tested compounds inhibited PRV replication, with the USP14 inhibitor b-AP15 exhibiting the most dramatic effect. Ablation of USP14 also influenced PRV replication, whereas replenishment of USP14 in null cells restored viral replication. Although inhibition of USP14 induced the K63-linked ubiquitination of PRV VP16 protein, its degradation was not dependent on the proteasome. USP14 directly bound to ubiquitin chains on VP16 through its UBL domain during the early stage of viral infection. Moreover, USP14 inactivation stimulated EIF2AK3/PERK- and ERN1/IRE1-mediated signaling pathways, which were responsible for VP16 degradation through SQSTM1/p62-mediated selective macroautophagy/autophagy. Ectopic expression of non-ubiquitinated VP16 fully rescued PRV replication. Challenge of mice with b-AP15 activated ER stress and autophagy and inhibited PRV infection . Our results suggested that USP14 was a potential therapeutic target to treat alphaherpesvirus-induced infectious diseases. ATF4: activating transcription factor 4; ATF6: activating transcription factor 6; ATG5: autophagy related 5; ATG12: autophagy related 12; CCK-8: cell counting kit-8; Co-IP: co-immunoprecipitation; CRISPR: clustered regulatory interspaced short palindromic repeat; Cas9: CRISPR associated system 9; DDIT3/CHOP: DNA-damage inducible transcript 3; DNAJB9/ERdj4: DnaJ heat shock protein family (Hsp40) member B9; DUBs: deubiquitinases; EIF2A/eIF2α: eukaryotic translation initiation factor 2A; EIF2AK3/PERK: eukaryotic translation initiation factor 2 alpha kinase 3; EP0: ubiquitin E3 ligase ICP0; ER: endoplasmic reticulum; ERN1/IRE1: endoplasmic reticulum (ER) to nucleus signaling 1; FOXO1: forkhead box O1; FRET: Förster resonance energy transfer; HSPA5/BiP: heat shock protein 5; HSV: herpes simplex virus; IE180: transcriptional regulator ICP4; MAP1LC3/LC3: microtube-associated protein 1 light chain 3; MOI: multiplicity of infection; MTOR: mechanistic target of rapamycin kinase; PPP1R15A/GADD34: protein phosphatase 1, regulatory subunit 15A; PRV: pseudorabies virus; PRV gB: PRV glycoprotein B; PRV gE: PRV glycoprotein E; qRT-PCR: quantitative real-time polymerase chain reaction; sgRNA: single guide RNA; siRNA: small interfering RNA; SQSTM1/p62: sequestosome 1; TCID: tissue culture infective dose; UB: ubiquitin; UBA: ubiquitin-associated domain; UBL: ubiquitin-like domain; UL9: DNA replication origin-binding helicase; UPR: unfolded protein response; USPs: ubiquitin-specific proteases; VHS: virion host shutoff; VP16: viral protein 16; XBP1: X-box binding protein 1; XBP1s: small XBP1; XBP1(t): XBP1-total.
Topics: Alphaherpesvirinae; Animals; Autophagy; Cell Proliferation; Endoplasmic Reticulum Stress; Herpes Simplex Virus Protein Vmw65; Macroautophagy; Mice; Sequestosome-1 Protein; Ubiquitin Thiolesterase
PubMed: 34822318
DOI: 10.1080/15548627.2021.2002101 -
Autophagy May 2023Alpha-herpesvirus causes lifelong infections and serious diseases in a wide range of hosts and has developed multiple strategies to counteract the host defense. Here, we...
Alpha-herpesvirus causes lifelong infections and serious diseases in a wide range of hosts and has developed multiple strategies to counteract the host defense. Here, we demonstrate that the tegument protein UL21 (unique long region 21) in pseudorabies virus (PRV) dampens type I interferon signaling by triggering the degradation of CGAS (cyclic GMP-AMP synthase) through the macroautophagy/autophagy-lysosome pathway. Mechanistically, the UL21 protein scaffolds the E3 ligase UBE3C (ubiquitin protein ligase E3C) to catalyze the K27-linked ubiquitination of CGAS at Lys384, which is recognized by the cargo receptor TOLLIP (toll interacting protein) and degraded in the lysosome. Additionally, we show that the N terminus of UL21 in PRV is dominant in destabilizing CGAS-mediated innate immunity. Moreover, viral tegument protein UL21 in herpes simplex virus type 1 (HSV-1) also displays the conserved inhibitory mechanisms. Furthermore, by using PRV, we demonstrate the roles of UL21 in degrading CGAS to promote viral infection . Altogether, these findings describe a distinct pathway where alpha-herpesvirus exploits TOLLIP-mediated selective autophagy to evade host antiviral immunity, highlighting a new interface of interplay between the host and DNA virus.: 3-MA: 3-methyladenine; ACTB: actin beta; AHV-1: anatid herpesvirus 1; ATG7: autophagy related 7; ATG13: autophagy related 13; ATG101: autophagy related 101; BHV-1: bovine alphaherpesvirus 1; BNIP3L/Nix: BCL2 interacting protein 3 like; CALCOCO2/NDP52: calcium binding and coiled-coil domain 2; CCDC50: coiled-coil domain containing 50; CCT2: chaperonin containing TCP1 subunit 2; CGAS: cyclic GMP-AMP synthase; CHV-2: cercopithecine herpesvirus 2; co-IP: co-immunoprecipitation; CQ: chloroquine; CRISPR: clustered regulatory interspaced short palindromic repeat; Cas9: CRISPR-associated system 9; CTD: C-terminal domain; Ctrl: control; DAPI: 4',6-diamidino-2-phenylindole; DBD: N-terminal DNA binding domain; DMSO: dimethyl sulfoxide; DYNLRB1: dynein light chain roadblock-type 1; EHV-1: equine herpesvirus 1; gB: glycoprotein B; GFP: green fluorescent protein; H&E: hematoxylin and eosin; HSV-1: herpes simplex virus 1; HSV-2: herpes simplex virus 2; IB: immunoblotting; IRF3: interferon regulatory factor 3; lenti: lentivirus; MAP1LC3/LC3: microtubule associated protein 1 light chain 3; MARCHF9: membrane associated ring-CH-type finger 9; MG132: cbz-leu-leu-leucinal; NBR1: NBR1 autophagy cargo receptor; NC: negative control; NEDD4L: NEDD4 like E3 ubiquitin protein ligase; NHCl: ammonium chloride; OPTN: optineurin; p-: phosphorylated; PFU: plaque-forming unit; Poly(dA:dT): Poly(deoxyadenylic-deoxythymidylic) acid; PPP1: protein phosphatase 1; PRV: pseudorabies virus; RB1CC1/FIP200: RB1 inducible coiled-coil 1; RNF126: ring finger protein 126; RT-PCR: real-time polymerase chain reaction; sgRNA: single guide RNA; siRNA: small interfering RNA; SQSTM1/p62: sequestosome 1; STING1: stimulator of interferon response cGAMP interactor 1; TBK1: TANK binding kinase 1; TOLLIP: toll interacting protein; TRIM33: tripartite motif containing 33; UL16: unique long region 16; UL21: unique long region 21; UL54: unique long region 54; Ub: ubiquitin; UBE3C: ubiquitin protein ligase E3C; ULK1: unc-51 like autophagy activating kinase 1; Vec: vector; VSV: vesicular stomatitis virus; VZV: varicella-zoster virus; WCL: whole-cell lysate; WT: wild-type; Z-VAD: carbobenzoxy-valyl-alanyl-aspartyl-[O-methyl]-fluoromethylketone.
Topics: Animals; Macroautophagy; Autophagy; Immunity, Innate; Nucleotidyltransferases; Ubiquitin-Protein Ligases; Viral Proteins
PubMed: 36343628
DOI: 10.1080/15548627.2022.2139921 -
Autophagy Nov 2021Increasing evidence suggests that induction of lethal macroautophagy/autophagy carries potential significance for the treatment of glioblastoma (GBM). In continuation of...
Increasing evidence suggests that induction of lethal macroautophagy/autophagy carries potential significance for the treatment of glioblastoma (GBM). In continuation of previous work, we demonstrate that pimozide and loperamide trigger an ATG5- and ATG7 (autophagy related 5 and 7)-dependent type of cell death that is significantly reduced with cathepsin inhibitors and the lipid reactive oxygen species (ROS) scavenger α-tocopherol in MZ-54 GBM cells. Global proteomic analysis after treatment with both drugs also revealed an increase of proteins related to lipid and cholesterol metabolic processes. These changes were accompanied by a massive accumulation of cholesterol and other lipids in the lysosomal compartment, indicative of impaired lipid transport/degradation. In line with these observations, pimozide and loperamide treatment were associated with a pronounced increase of bioactive sphingolipids including ceramides, glucosylceramides and sphingoid bases measured by targeted lipidomic analysis. Furthermore, pimozide and loperamide inhibited the activity of SMPD1/ASM (sphingomyelin phosphodiesterase 1) and promoted induction of lysosomal membrane permeabilization (LMP), as well as release of CTSB (cathepsin B) into the cytosol in MZ-54 wild-type (WT) cells. Whereas LMP and cell death were significantly attenuated in and knockout (KO) cells, both events were enhanced by depletion of the lysophagy receptor VCP (valosin containing protein), supporting a pro-survival function of lysophagy under these conditions. Collectively, our data suggest that pimozide and loperamide-driven autophagy and lipotoxicity synergize to induce LMP and cell death. The results also support the notion that simultaneous overactivation of autophagy and induction of LMP represents a promising approach for the treatment of GBM.: ACD: autophagic cell death; AKT1: AKT serine/threonine kinase 1; ATG5: autophagy related 5; ATG7: autophagy related 7; ATG14: autophagy related 14; CERS1: ceramide synthase 1; CTSB: cathepsin B; CYBB/NOX2: cytochrome b-245 beta chain; ER: endoplasmatic reticulum; FBS: fetal bovine serum; GBM: glioblastoma; GO: gene ontology; HTR7/5-HT7: 5-hydroxytryptamine receptor 7; KD: knockdown; KO: knockout; LAMP1: lysosomal associated membrane protein 1; LAP: LC3-associated phagocytosis; LMP: lysosomal membrane permeabilization; MAP1LC3B: microtubule associated protein 1 light chain 3 beta; MTOR: mechanistic target of rapamycin kinase; RB1CC1: RB1 inducible coiled-coil 1; ROS: reactive oxygen species; RPS6: ribosomal protein S6; SMPD1/ASM: sphingomyelin phosphodiesterase 1; VCP/p97: valosin containing protein; WT: wild-type.
Topics: Autophagy; Autophagy-Related Protein 5; Autophagy-Related Protein 7; Brain Neoplasms; Cathepsins; Cell Death; Cell Line, Tumor; Ceramides; Gene Knockout Techniques; Glioblastoma; Humans; Lipid Metabolism; Loperamide; Lysosomes; Permeability; Pimozide; Proteome; Sphingomyelin Phosphodiesterase
PubMed: 33461384
DOI: 10.1080/15548627.2021.1874208