2025-05-12 九州大学
<関連情報>
- https://www.kyushu-u.ac.jp/ja/researches/view/1263
- https://www.kyushu-u.ac.jp/f/61646/25_0513_01.pdf
- https://rupress.org/jcb/article/224/7/e202408166/277925/The-mitophagy-receptors-BNIP3-and-NIX-mediate
マイトファジーの受容体BNIP3とNIXが、ミトコンドリアへの隔離膜の強固な接着と拡張を媒介する
The mitophagy receptors BNIP3 and NIX mediate tight attachment and expansion of the isolation membrane to mitochondria
Shun-ichi Yamashita,Ritsuko Arai,Hiroshi Hada,Benjamin Scott Padman,Michael Lazarou,David C. Chan,Tomotake Kanki,Satoshi Waguri
Journal of Cell Biology Published:May 13 2025
DOI:https://doi.org/10.1083/jcb.202408166
BNIP3 and NIX are the main receptors for mitophagy, but their mechanisms of action remain elusive. Here, we used correlative light EM (CLEM) and electron tomography to reveal the tight attachment of isolation membranes (IMs) to mitochondrial protrusions, often connected with ER via thin tubular and/or linear structures. In BNIP3/NIX-double knockout (DKO) HeLa cells, the ULK1 complex and nascent IM formed on mitochondria, but the IM did not expand. Artificial tethering of LC3B to mitochondria induced mitophagy that was equally efficient in DKO cells and WT cells. BNIP3 and NIX accumulated at the segregated mitochondrial protrusions via binding with LC3 through their LIR motifs but did not require dimer formation. Finally, the average distance between the IM and the mitochondrial surface in receptor-mediated mitophagy was significantly smaller than that in ubiquitin-mediated mitophagy. Collectively, these results indicate that BNIP3 and NIX are required for the tight attachment and expansion of the IM along the mitochondrial surface during mitophagy.
