Interaction between PI3K and the VDAC2 channel tethers Ras-PI3K-positive endosomes to mitochondria and promotes endosome maturation
Interaction between PI3K and the VDAC2 channel tethers Ras-PI3K-positive endosomes to mitochondria and promotes endosome maturation
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PI3K 和 VDAC2 通道之间的相互作用将 Ras-PI3K 阳性核内体束缚到线粒体并促进核内体成熟
DOI：
10.1016/j.celrep.2023.112229
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发表时间：
2023
期刊：
影响因子：
8.8
通讯作者：
Ohba Yusuke
中科院分区：
文献类型：
--
作者：
Satoh Aya O.;Fujioka Yoichiro;Kashiwagi Sayaka;Yoshida Aiko;Fujioka Mari;Sasajima Hitoshi;Nanbo Asuka;Amano Maho;Ohba Yusuke
哺乳动物细胞的细胞内细胞器在各种细胞过程中相互通信。然而，这种细胞器间联系的功能和分子机制在很大程度上仍不清楚。在这里，我们确定电压依赖性阴离子通道2（VDAC 2），线粒体外膜蛋白，作为磷酸肌醇3-激酶（PI 3 K）的结合伴侣，一个调节器的网格蛋白非依赖性胞吞下游的小GT3 Ras。VDAC 2响应于表皮生长因子的细胞刺激将Ras-PI 3 K复合物阳性的内体拴系到线粒体，并促进网格蛋白非依赖性内吞作用以及膜结合位点处的内体成熟。利用光遗传学系统诱导内体-内体结合，我们发现，除了其在这种结合中的结构作用之外，VDAC 2在功能上涉及促进内体成熟。因此，内吞体-内体缔合在不依赖网格蛋白的内吞作用和内体成熟的调节中起作用。
Intracellular organelles of mammalian cells communicate with one another during various cellular processes. The functions and molecular mechanisms of such interorganelle association remain largely unclear, however. We here identify voltage-dependent anion channel 2 (VDAC2), a mitochondrial outer membrane protein, as a binding partner of phosphoinositide 3-kinase (PI3K), a regulator of clathrin-independent endocytosis downstream of the small GTPase Ras. VDAC2 tethers endosomes positive for the Ras-PI3K complex to mitochondria in response to cell stimulation with epidermal growth factor and promotes clathrin-independent endocytosis, as well as endosome maturation at membrane association sites. With an optogenetics system to induce mitochondrion-endosome association, we find that, in addition to its structural role in such association, VDAC2 is functionally implicated in the promotion of endosome maturation. The mitochondrion-endosome association thus plays a role in the regulation of clathrin-independent endocytosis and endosome maturation.