Inhibition of PIKfyve Leads to Lysosomal Disorders via Dysregulation of mTOR Signaling

Inhibition of PIKfyve Leads to Lysosomal Disorders via Dysregulation of mTOR Signaling

Blog Article

PIKfyve is an endosomal lipid kinase that synthesizes phosphatidylinositol 3,5-biphosphate from phosphatidylinositol 3-phsphate.Inhibition of PIKfyve activity leads to lysosomal enlargement and cytoplasmic vacuolation, attributed to impaired lysosomal fission processes and homeostasis.However, the precise molecular mechanisms underlying these Drone effects remain a topic of debate.In this study, we present findings from PIKfyve-deficient zebrafish embryos, revealing enlarged macrophages with giant vacuoles reminiscent of lysosomal storage disorders.

Treatment with mTOR inhibitors or effective knockout of mTOR partially reverses these abnormalities and extend the lifespan of mutant larvae.Further in vivo and in vitro mechanistic investigations provide evidence that PIKfyve activity is essential for mTOR shutdown during early zebrafish development and in cells cultured under serum-deprived conditions.These findings underscore the critical role of PIKfyve activity in regulating mTOR signaling balance bikes and suggest potential therapeutic applications of PIKfyve inhibitors for the treatment of lysosomal storage disorders.