Loss of ATP13A2 function leads to lysosomal polyamine sequestration, depleting cytosolic polyamines in astrocytes. This triggers compensatory polyamine biosynthesis, diverting SAM from DNA methylation and promoting neuroinflammation.
Cellular polyamine depletion for cancer treatment is hindered by compensatory uptake. ATP13A3, not ATP13A2, is the key polyamine importer affected by DFMO. Antizyme inhibits uptake by ATP13A3, suggesting a targetable strategy for cancer therapy.
Assay for NBD-labeled lipid uptake in HeLa-CDC50A-OE cells includes seeding, transfection, and flow cytometry to measure flippase construct activity, enabling quantitative assessment of lipid uptake.
