ASAP1和ARF1通过调节mTOR重激活调控自噬性溶酶体再生

ASAP1 and ARF1 Control of Autophagic Lysosome Reformation through Regulating mTOR Reactivation

自噬是一种在进化上保守的溶酶体依赖的降解途径.在缺乏营养的条件下,细胞会产生自噬体与溶酶体融合形成自噬溶酶体,并会通过自噬来降解自身物质.之后溶酶体会从自噬溶酶体再生,这个进化上保守的过程称为自噬性溶酶体再生(ALR),该过程由长时程饥饿中mTOR重激活引起.我们课题组在之前的研究工作中筛选出ARF1的GAP蛋白ASAP1参与调解ALR.本文在之前工作的基础上,发现ARF1会在ALR过程中转位到自噬溶酶体上.敲低ASAP1或者过表达连有GFP标签的ARF1的GTP形式,会抑制mTOR的重激活以及ALR.因此,ARF1以及ASAP1是通过调节mTOR的重激活而调控ALR发生.

Autophagy is an evolutionarily conserved lysosome-based degradation process. Stimuli such as nutrients starvation induce formation of autophagosome, which then fuse with lysosome to form autolysosome. After degradation of engulfed cellular content, lysosomes are recycled from autolysosomes through an evolutionarily conserved process named autophagic lysosome reformation （ALR）, which is triggered by reactivation of mTOR during prolonged starvation. Our previous study identified ASAP1, the GAP protein for ARF1, is a regulator of ALR. In this study, we report that ARF1 is translocated to autolysosome during ALR. Knocking down ASAP1, or overexpression GTP binding form of ARF1, can block the mTOR reactivation and ALR. Thus, ARF1 and ASAP1 regulate ALR through regulating mTOR reactivation.