Rab GTPase 调控线粒体自噬的分子机制研究

选择性自噬通过清除细胞内受损的细胞器等冗余的物质维持细胞稳态。自噬小体通过选择性自噬受体实现对底物的特异性识别和包裹，进而通过形成自噬溶酶体将底物降解。但是，选择性自噬过程中自噬小体形成的早期事件调控机制尚不清楚。我们最近研究发现：一些Rab GTPase部分通过自噬通路降解，这一现象类似于LC3-II；在这些Rab GTPase中，有一部分和线粒体自噬受体互作，并被招募到去极化的线粒体；敲低Rab GTPase的表达造成受损线粒体的累积。因此我们提出科学假设：Rab GTPase和线粒体自噬受体的互作调控线粒体自噬的早期阶段。基于前期结果，我们将进一步研究Rab GTPase如何调控线粒体自噬。相关研究结果将有助于我们阐明选择性自噬起始的调控机制。

Selective autophagy controls cellular homeostasis by eliminating unwanted cytoplasmic materials including damaged organelles. Selective autophagy receptors ensure specific recognition and sequestration of their designated cargoes within autophagosomes for subsequent lysosomal breakdown. It remains unclear how the initial steps of autophagosome biogenesis is regulated during selective autophagy. Our recent study indicated that a group of human Rab GTPases are partially degraded through autophagy pathway in a manner similar to LC3-II; some of these GTPases interact with mitophagy receptors and are recruited to depolarized mitochondria；the depletion of one of these Rab GTPase resultes in accumulation of damaged mitochondria. Therefore, we hypothesize that the interaction of these Rab GTPases with mitophagy receptors regulates the early steps of mitophagy. Based on the preliminary results, we will further investigate how these Rab GTPases regulate mitophagy. Our findings from this project should be helpful to elucidate mechanisms that are involved in the initiation of selective autophagy.