Lysosomal Fusion: An Efficient Mechanism Increasing Their Sequestration Capacity for Weak Base Drugs without Apparent Lysosomal Biogenesis
نویسندگان
چکیده
منابع مشابه
Lysosomal sequestration of hydrophobic weak base chemotherapeutics triggers lysosomal biogenesis and lysosome-dependent cancer multidrug resistance
Multidrug resistance (MDR) is a primary hindrance to curative cancer chemotherapy. In this respect, lysosomes were suggested to play a role in intrinsic MDR by sequestering protonated hydrophobic weak base chemotherapeutics away from their intracellular target sites. Here we show that intrinsic resistance to sunitinib, a hydrophobic weak base tyrosine kinase inhibitor known to accumulate in lys...
متن کاملLysosomal sequestration of sunitinib: a novel mechanism of drug resistance.
PURPOSE Resistance to antiangiogenic tyrosine kinase inhibitors such as sunitinib is an important clinical problem, but its underlying mechanisms are largely unknown. We analyzed tumor sunitinib levels in mice and patients and studied sensitivity and resistance mechanisms to sunitinib. EXPERIMENTAL DESIGN Intratumoral and plasma sunitinib concentrations in mice and patients were determined. S...
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The acid sphingomyelinase (ASMase) localizes to the lumen of endosomes, phagosomes and lysosomes as well as to the outer leaflet of the plasma membrane and hydrolyses sphingomyelin to ceramide and phosphorylcholine. Using the facultative intracellular bacterium Listeria monocytogenes, we show that maturation of phagosomes into phagolysosomes is severely impaired in macrophages genetically defic...
متن کاملLysosomal accumulation of anticancer drugs triggers lysosomal exocytosis
We have recently shown that hydrophobic weak base anticancer drugs are highly sequestered in acidic lysosomes, inducing TFEB-mediated lysosomal biogenesis and markedly increased lysosome numbers per cell. This enhanced lysosomal sequestration of chemotherapeutics, away from their intracellular targets, provoked cancer multidrug resistance. However, little is known regarding the fate of lysosome...
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Compartmentalization is essential in the eukaryotic cell and this is most often achieved by sequestering specific components that perform a related function in a membrane-bound organelle. To function normally these organelles must transiently fuse with other compartments in order to transfer protein and lipid that is needed for them to function. These events must be highly coordinated otherwise...
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ژورنال
عنوان ژورنال: Biomolecules
سال: 2020
ISSN: 2218-273X
DOI: 10.3390/biom10010077