TI - FIP200 functions downstream of mammalian target of rapamycin ( mTOR ) in autophagosome formation . AB - FIP200 interacts with TSC1 and inhibits its function . The TSC1-TSC2 heterodimer inhibits mTOR function through Rheb inactivation . As autophagy is negatively regulated by mTOR signaling ( Meijer and Codogno , 2004 ) , we investigated whether the autophagy defect of FIP200-/- MEFs is a result of aberrant TSC-mTOR signaling . If this were the case , autophagy should be induced by treatment with the mTOR inhibitor rapamycin . In wild-type MEFs , rapamycin induced LC3 conversion both in the absence and presence of bafilomycin A1 . However , the LC3 conversion induced by rapamycin was still impaired in FIP200-/- MEFs ( Fig 7 A ) . We also observed that rapamycin was able to induce GFP-Atg5 and GFP-LC3 dot formation in wild-type MEFs but not in FIP200-/- MEFs ( Fig 7 B ) . Furthermore , mTOR appeared to be normally suppressed in FIP200-/- MEFs after serum and amino acid starvation , as judged by 4E-BP1 dePHOSphorylation , despite the suppression of autophagy ( Fig 5 A ) . Collectively , these data suggest that the defect in autophagosome formation of FIP200-/- MEFs is caused by loss of FIP200 function downstream of mTOR and not by aberrant nutrient signaling including the TSC complex . FIP200-/- MEFs were also resistant to various autophagy-inducing reagents such as lithium chloride and ceramide . Because the effect of lithium is independent of mTOR , FIP200 should function in both mTOR -dependent and -independent autophagy .