ULK 1 translocates to mitochondria and phosphorylates FUNDC 1 to regulate mitophagy
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| المؤلفون: | Liangqing Zhang, Wen Li, Lei Huang, Guo Chen, Longxuan Li, Sen-Fang Sui, Wenxian Wu, Weili Tian, Bin Zhao, Du Feng, Changqian Zhou, Zhe Hu, Xingli Zhang, Yushan Zhu, Peng Xue, Lei Liu, Xingliang Zhang |
| المصدر: | EMBO reports. 15:566-575 |
| بيانات النشر: | EMBO, 2014. |
| سنة النشر: | 2014 |
| مصطلحات موضوعية: | Mitochondrial Degradation, Plasma protein binding, Protein Serine-Threonine Kinases, Mitochondrion, Biology, Biochemistry, Mitochondrial Proteins, Mitophagy, Genetics, Autophagy-Related Protein-1 Homolog, Humans, Phosphorylation, Molecular Biology, Scientific Reports, Autophagy, Intracellular Signaling Peptides and Proteins, Membrane Proteins, ULK1, Cell Hypoxia, Mitochondria, Up-Regulation, Cell biology, Mutation, Microtubule-Associated Proteins, HeLa Cells, Protein Binding |
| الوصف: | Autophagy eliminates dysfunctional mitochondria in an intricate process known as mitophagy. ULK1 is critical for the induction of autophagy, but its substrate(s) and mechanism of action in mitophagy remain unclear. Here, we show that ULK1 is upregulated and translocates to fragmented mitochondria upon mitophagy induction by either hypoxia or mitochondrial uncouplers. At mitochondria, ULK1 interacts with FUNDC1, phosphorylating it at serine 17, which enhances FUNDC1 binding to LC3. A ULK1-binding-deficient mutant of FUNDC1 prevents ULK1 translocation to mitochondria and inhibits mitophagy. Finally, kinase-active ULK1 and a phospho-mimicking mutant of FUNDC1 rescue mitophagy in ULK1-null cells. Thus, we conclude that FUNDC1 regulates ULK1 recruitment to damaged mitochondria, where FUNDC1 phosphorylation by ULK1 is crucial for mitophagy. |
| تدمد: | 1469-3178 1469-221X |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::f835f718399d2c8c8fd89ffbb2a5f491Test https://doi.org/10.1002/embr.201438501Test |
| حقوق: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....f835f718399d2c8c8fd89ffbb2a5f491 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 14693178 1469221X |
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