Inhibition of lipid kinase PIKfyve reveals a role for phosphatase Inpp4b in the regulation of PI(3)P-mediated lysosome dynamics through VPS34 activity

Abemaciclib and Vacuolin-1 decrease aggregate-prone TDP-43 accumulation by accelerating autophagic flux

“…Previous studies suggested that the inhibition of PIKfyve facilitated vesicle fusion through increases in PI(3)P levels [ 22 ]. To clarify whether Abe and Vac increased PI(3)P levels, we prepared HeLa cells stably expressing the GFP-tagged 2 × FYVE domain, a marker for PI(3)P [ 23 ].…”

“…PI(3)P is an autophagy inducer [ 16 ]. On the other hand, the hyperactivation of VPS34 was previously shown to induce the extensive formation of vacuole-like autolysosomes [ 22 ]. The results of our reporter assay using the fluorescent protein-tagged 2 × FYVE domain indicated that PI(3)P localizes to vacuole-like autolysosomes.…”

“…On the other hand, a previous study indicated that a PIKfyve inhibitor time-dependently suppressed autophagic flux [ 36 ]. Vacuoles induced by PIKfyve inhibitors were formed by autophagosomes and lysosomes [ 7 , 22 ], and the inhibition of PIKfyve decreased lysosome numbers [ 37 ]. Therefore, the depletion of autophagosomes or lysosomes due to excessive autophagosome-lysosome fusion through the inhibition of PIKfyve may suppress autophagic flux.…”