Fig. 8

A schematic of autophagy modulation in dystrophin-deficient myoblasts. PTEN was found to be highly expressed in dystrophin-deficient myoblasts which leads to the reduction of activation of PI3K. Surprisingly, Akt was found not to be activated due to the inactivation of Rictor-mTORC2. Furthermore, downstream of Akt, i.e. p70S6K and FoxO3, there was defective activation. Activation of p70S6K was reduced, indicating that protein synthesis regulation is impaired. FoxO3 (unphosphorylated) expression accumulated thus increased FoxO3 nuclear translocation. Accumulation of translocated-FoxO3 to the nucleus increases the expression of autophagy related proteins, i.e. Atg5, Atg7, Beclin1. As a result, phagophore formation is increased and the maturation of autophagosome by Atgs; however, autophagic flux is reduced. The perturbation of PI3K/Akt increases nuclear-FoxO3, thus modulating excessive autophagosome formation while reducing autophagic flux in dystrophin-deficient myoblasts