| Online-Ressource |
Verfasst von: | Chen, Chih-Wei [VerfasserIn]  |
| Su, Chi [VerfasserIn]  |
| Huang, Chang-Yu [VerfasserIn]  |
| Huang, Xuan-Rong [VerfasserIn]  |
| Cuili, Xiaojing [VerfasserIn]  |
| Chao, Tung [VerfasserIn]  |
| Fan, Chun-Hsiang [VerfasserIn]  |
| Ting, Cheng-Wei [VerfasserIn]  |
| Tsai, Yi-Wei [VerfasserIn]  |
| Yang, Kai-Chien [VerfasserIn]  |
| Yeh, Ti-Yen [VerfasserIn]  |
| Hsieh, Sung-Tsang [VerfasserIn]  |
| Chen, Yi-Ju [VerfasserIn]  |
| Feng, Yuxi [VerfasserIn]  |
| Hunter, Tony [VerfasserIn]  |
| Chang, Zee-Fen [VerfasserIn]  |
Titel: | NME3 is a gatekeeper for DRP1-dependent mitophagy in hypoxia |
Verf.angabe: | Chih-Wei Chen, Chi Su, Chang-Yu Huang, Xuan-Rong Huang, Xiaojing Cuili, Tung Chao, Chun-Hsiang Fan, Cheng-Wei Ting, Yi-Wei Tsai, Kai-Chien Yang, Ti-Yen Yeh, Sung-Tsang Hsieh, Yi-Ju Chen, Yuxi Feng, Tony Hunter & Zee-Fen Chang |
E-Jahr: | 2024 |
Jahr: | 13 March 2024 |
Umfang: | 20 S. |
Illustrationen: | Illustrationen |
Fussnoten: | Gesehen am 27.11.2024 |
Titel Quelle: | Enthalten in: Nature Communications |
Ort Quelle: | [London] : Springer Nature, 2010 |
Jahr Quelle: | 2024 |
Band/Heft Quelle: | 15(2024), Artikel-ID 2264, Seite 1-20 |
ISSN Quelle: | 2041-1723 |
Abstract: | NME3 is a member of the nucleoside diphosphate kinase (NDPK) family localized on the mitochondrial outer membrane (MOM). Here, we report a role of NME3 in hypoxia-induced mitophagy dependent on its active site phosphohistidine but not the NDPK function. Mice carrying a knock-in mutation in the Nme3 gene disrupting NME3 active site histidine phosphorylation are vulnerable to ischemia/reperfusion-induced infarction and develop abnormalities in cerebellar function. Our mechanistic analysis reveals that hypoxia-induced phosphatidic acid (PA) on mitochondria is essential for mitophagy and the interaction of DRP1 with NME3. The PA binding function of MOM-localized NME3 is required for hypoxia-induced mitophagy. Further investigation demonstrates that the interaction with active NME3 prevents DRP1 susceptibility to MUL1-mediated ubiquitination, thereby allowing a sufficient amount of active DRP1 to mediate mitophagy. Furthermore, MUL1 overexpression suppresses hypoxia-induced mitophagy, which is reversed by co-expression of ubiquitin-resistant DRP1 mutant or histidine phosphorylatable NME3. Thus, the site-specific interaction with active NME3 provides DRP1 a microenvironment for stabilization to proceed the segregation process in mitophagy. |
DOI: | doi:10.1038/s41467-024-46385-7 |
URL: | Bitte beachten Sie: Dies ist ein Bibliographieeintrag. Ein Volltextzugriff für Mitglieder der Universität besteht hier nur, falls für die entsprechende Zeitschrift/den entsprechenden Sammelband ein Abonnement besteht oder es sich um einen OpenAccess-Titel handelt.
kostenfrei: Volltext: https://doi.org/10.1038/s41467-024-46385-7 |
| kostenfrei: Volltext: https://www.nature.com/articles/s41467-024-46385-7 |
| DOI: https://doi.org/10.1038/s41467-024-46385-7 |
Datenträger: | Online-Ressource |
Sprache: | eng |
Sach-SW: | Mechanisms of disease |
| Mitophagy |
| Phosphorylation |
K10plus-PPN: | 1909611662 |
Verknüpfungen: | → Zeitschrift |
NME3 is a gatekeeper for DRP1-dependent mitophagy in hypoxia / Chen, Chih-Wei [VerfasserIn]; 13 March 2024 (Online-Ressource)