Vimentin regulates mTORC1 signaling by facilitating mTORC1 localization to lysosomes.

A simplified scheme of the mTORC1 signaling system. Our results demonstrate that in the presence of nutrients, vimentin facilitates mTORC1 activation by regulating Rag GTPase activation. This results in the phosphorylation of 4EBP1 and P70S6K downstream targets, which lead to protein synthesis. Moreover, activation of mTORC1 results in decreased autophagy, as demonstrated by higher levels of the autophagic flux indicator p62 and reduced LC3I conversion to LC3II. As this autophagy inhibition works even under nutrient-starved condition, in the absence of AKT activation, the results imply that vimentin inhibits autophagy by mTORC1-mediated inhibition of ULK1-Beclin pathway. In this way, vimentin promotes cell size in 2 directions: by boosting protein synthesis through mTORC1 activation and by inhibiting of protein degradation through inhibition of autophagic flux. mTORC1, mechanistic target of rapamycin kinase complex 1.