The mitophagy receptors BNIP3 and NIX mediate tight attachment and expansion of the isolation membrane to mitochondria

Yamashita, SI; Arai, R; Hada, H; Padman, BS; Lazarou, M; Chan, DC; Kanki, T; Waguri, S

Author(s): Yamashita, SI; Arai, R; Hada, H; Padman, BS; Lazarou, M; Chan, DC; Kanki, T; Waguri, S;
Details: Publication Year 2025-07-07,Volume 224,Issue #7,Page e202408166
Journal Title: Journal of Cell Biology
Abstract: 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.
Publisher: Rockefeller University Press
Keywords: Humans; *Mitophagy; HeLa Cells; *Membrane Proteins/metabolism/genetics; *Proto-Oncogene Proteins/metabolism/genetics; *Mitochondrial Proteins/metabolism/genetics; *Mitochondria/metabolism/ultrastructure/genetics; *Mitochondrial Membranes/metabolism/ultrastructure; *Tumor Suppressor Proteins/metabolism/genetics; Microtubule-Associated Proteins/metabolism/genetics; Autophagy-Related Protein-1 Homolog/metabolism/genetics; Intracellular Signaling Peptides and Proteins/metabolism/genetics
Research Division(s): Ubiquitin Signalling
PubMed ID: 40358358
Publisher's Version: https://doi.org/10.1083/jcb.202408166
Open Access at Publisher's Site: https://doi.org/10.1083/jcb.202408166
Terms of Use/Rights Notice: Refer to copyright notice on published article.

Creation Date: 2025-05-29 02:03:41

Last Modified: 2025-05-29 02:08:05