Reconstitution of BNIP3/NIX-mitophagy initiation reveals hierarchical flexibility of the autophagy machinery
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Zenodo
2025
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| _version_ | 1866902330389037056 |
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| author | Adriaenssens, Elias Schaar, Stefan Cook, Zeke Stuck, Jan F.M. Sawa-Makarska, Justyna Nguyen, Thanh Ngọc Ren, Xuefen Schuschnig, Martina Romanov, Julia Khuu, Grace Uoselis, Louise Lazarou, Michael Hummer, Gerhard Hurley, James Martens, Sascha |
| author_facet | Adriaenssens, Elias Schaar, Stefan Cook, Zeke Stuck, Jan F.M. Sawa-Makarska, Justyna Nguyen, Thanh Ngọc Ren, Xuefen Schuschnig, Martina Romanov, Julia Khuu, Grace Uoselis, Louise Lazarou, Michael Hummer, Gerhard Hurley, James Martens, Sascha |
| contents | <p><span>Selective autophagy is a lysosomal degradation pathway that is critical for maintaining cellular homeostasis by disposing of harmful cellular material. While the mechanisms by which soluble cargo receptors recruit the autophagy machinery are becoming increasingly clear, the principles governing how organelle-localized transmembrane cargo receptors initiate selective autophagy remain poorly understood. Here, we demonstrate that transmembrane cargo receptors can initiate autophagosome biogenesis not only by recruiting the upstream FIP200/ULK1 complex but also via a WIPI-ATG13 complex. This latter pathway is employed by the BNIP3/NIX receptors to trigger mitophagy. Additionally, other transmembrane mitophagy receptors, including FUNDC1 and BCL2L13, exclusively use the FIP200/ULK1 complex, while FKBP8 and the ER-phagy receptor TEX264 are capable of utilising both pathways to initiate autophagy. Our study defines the molecular rules for initiation by transmembrane cargo receptors, revealing remarkable flexibility in the assembly and activation of the autophagy machinery, with significant implications for therapeutic interventions.</span></p> |
| format | Recurso digital |
| id | zenodo_https___doi_org_10_5281_zenodo_15109147 |
| institution | Zenodo |
| language | |
| publishDate | 2025 |
| publisher | Zenodo |
| record_format | zenodo |
| spellingShingle | Reconstitution of BNIP3/NIX-mitophagy initiation reveals hierarchical flexibility of the autophagy machinery Adriaenssens, Elias Schaar, Stefan Cook, Zeke Stuck, Jan F.M. Sawa-Makarska, Justyna Nguyen, Thanh Ngọc Ren, Xuefen Schuschnig, Martina Romanov, Julia Khuu, Grace Uoselis, Louise Lazarou, Michael Hummer, Gerhard Hurley, James Martens, Sascha <p><span>Selective autophagy is a lysosomal degradation pathway that is critical for maintaining cellular homeostasis by disposing of harmful cellular material. While the mechanisms by which soluble cargo receptors recruit the autophagy machinery are becoming increasingly clear, the principles governing how organelle-localized transmembrane cargo receptors initiate selective autophagy remain poorly understood. Here, we demonstrate that transmembrane cargo receptors can initiate autophagosome biogenesis not only by recruiting the upstream FIP200/ULK1 complex but also via a WIPI-ATG13 complex. This latter pathway is employed by the BNIP3/NIX receptors to trigger mitophagy. Additionally, other transmembrane mitophagy receptors, including FUNDC1 and BCL2L13, exclusively use the FIP200/ULK1 complex, while FKBP8 and the ER-phagy receptor TEX264 are capable of utilising both pathways to initiate autophagy. Our study defines the molecular rules for initiation by transmembrane cargo receptors, revealing remarkable flexibility in the assembly and activation of the autophagy machinery, with significant implications for therapeutic interventions.</span></p> |
| title | Reconstitution of BNIP3/NIX-mitophagy initiation reveals hierarchical flexibility of the autophagy machinery |
| url | https://doi.org/10.5281/zenodo.15109147 |