mTOR interacts with AIF to positively regulate autophagy

Abstract

Abstract The mechanism of the positive regulation of autophagy by mammalian target of rapamycin (mTOR) remains largely unknown. In the present study, we observed that inhibition of mTOR either genetically or pharmacologically suppressed basal and H2O2-induced autophagic processes concomitant with marked upregulation of apoptosis inducing factor (AIF) expression. In cells with mTOR knockdown, deprivation of AIF partially rescued both basal and induced autophagy. Importantly, we found that AIF interacted with either mTOR or Beclin1 and that AIF loss markedly enhanced the association of Beclin1 with VPS34, which is essential for autophagy initiation. In contrast, mTOR loss increased the binding of AIF to Beclin1, concomitantly decreasing the interaction between Beclin1 and VPS34. Collectively, the data presented here revealed a previously unnoticed autophagic regulatory pathway in which mTOR functioned as a positive regulator by directly interacting with AIF and autophagic proteins.