ナノマシンが細胞内の清掃を行う様子を明らかにしました。 Researchers reveal how a nanomachine takes care of cleaning up inside the cell
2023-05-23 マックス・プランク研究所
◆ドイツの研究チームが、オートファゴソームの組み立て過程を初めて観察し、その仕組みを解明した。この研究は将来の治療薬開発に役立つ可能性があり、オートファジーに関連する疾患の治療に貢献することが期待されている。
<関連情報>
- https://www.mpg.de/20342610/0522-bich-blick-ins-herz-der-zellulaeren-muellabfuhr-17216463-x
- https://www.sciencedirect.com/science/article/pii/S1097276523003210?via%3Dihub
ヒトのオートファジーの開始と脂質移動の基礎となるメタモルフィックタンパク質 Metamorphic proteins at the basis of human autophagy initiation and lipid transfer
Anh Nguyen, Francesca Lugarini, Céline David, Pouya Hosnani, Çağla Alagöz, Annabelle Friedrich, David Schlütermann, Barbora Knotkova, Anoshi Patel, Iwan Parfentev, Henning Urlaub, Michael Meinecke, Björn Stork, Alex C. Faesen
Mol Cell Published: May 19, 2023
DOI:https://doi.org/10.1016/j.molcel.2023.04.026
Highlights
•Purified autophagy initiation subcomplexes self-assemble in a supercomplex
•ATG9-13-101 is an assembly platform of supercomplex by recruiting each subcomplex
•Metamorphosis of ATG13 and ATG101 is rate limiting for ATG9-13-101 assembly
•Lipid transfer by ATG2 is accelerated by ATG9 and ATG13-101
Summary
Autophagy is a conserved intracellular degradation pathway that generates de novo double-membrane autophagosomes to target a wide range of material for lysosomal degradation. In multicellular organisms, autophagy initiation requires the timely assembly of a contact site between the ER and the nascent autophagosome. Here, we report the in vitro reconstitution of a full-length seven-subunit human autophagy initiation supercomplex built on a core complex of ATG13-101 and ATG9. Assembly of this core complex requires the rare ability of ATG13 and ATG101 to switch between distinct folds. The slow spontaneous metamorphic conversion is rate limiting for the self-assembly of the supercomplex. The interaction of the core complex with ATG2-WIPI4 enhances tethering of membrane vesicles and accelerates lipid transfer of ATG2 by both ATG9 and ATG13-101. Our work uncovers the molecular basis of the contact site and its assembly mechanisms imposed by the metamorphosis of ATG13-101 to regulate autophagosome biogenesis in space and time.
