Atg13 and FIP200 act independently of Ulk1 and Ulk2 in autophagy induction
Sebastian Alers,Antje S. Löffler,Florian Paasch,Alexandra M. Dieterle,Hildegard Keppeler,Kirsten Lauber,David G. Campbell,Birgit Fehrenbacher,Martin Schaller,Sebastian Wesselborg,Björn Stork +10 more
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TLDR
In this paper, Atg13 has been shown to be indispensable for autophagy induction in Atg-deficient cells, and the simultaneous knockout of Ulk1 and Ulk2 did not have a similar effect on autophagia induction.Abstract:
Under normal growth conditions the mammalian target of rapamycin complex 1 (mTORC1) negatively regulates the central autophagy regulator complex consisting of Unc-51-like kinases 1/2 (Ulk1/2), focal adhesion kinase family-interacting protein of 200 kDa (FIP200) and Atg13. Upon starvation, mTORC1-mediated repression of this complex is released, which then leads to Ulk1/2 activation. In this scenario, Atg13 has been proposed as an adaptor mediating the interaction between Ulk1/2 and FIP200 and enhancing Ulk1/2 kinase activity. Using Atg13-deficient cells, we demonstrate that Atg13 is indispensable for autophagy induction. We further show that Atg13 function strictly depends on FIP200 binding. In contrast, the simultaneous knockout of Ulk1 and Ulk2 did not have a similar effect on autophagy induction. Accordingly, the Ulk1-dependent phosphorylation sites we identified in Atg13 are expendable for this process. This suggests that Atg13 has an additional function independent of Ulk1/2 and that Atg13 and FIP200 act in concert during autophagy induction.read more
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Atg13 is essential for autophagy and cardiac development in mice
Takeshi Kaizuka,Noboru Mizushima +1 more
TL;DR: The results suggest that Atg13 has both autophagic and nonautophagic functions and that the latter are essential for cardiac development and likely shared with FIP200 but not with ULK1/2.
Journal ArticleDOI
So Many Roads: the Multifaceted Regulation of Autophagy Induction.
TL;DR: It is illustrated that rather than thinking of autophagy as a linear pathway, it is better to think of autophileagy induction as an interconnecting web of key regulators, many of which can induce autophile through different requirements depending on the type and length of induction signals.
Journal ArticleDOI
Selective Autophagy of Mitochondria on a Ubiquitin-Endoplasmic-Reticulum Platform
Maria Zachari,Sigurdur Runar Gudmundsson,Ziyue Li,Maria Manifava,Ronak Shah,Matthew D. Smith,James Stronge,Eleftherios Karanasios,Caterina Piunti,Chieko Kishi-Itakura,Helena Vihinen,Eija Jokitalo,Jun-Lin Guan,Folma Buss,Andrew M. Smith,Simon Walker,Eeva-Liisa Eskelinen,Nicholas T. Ktistakis +17 more
TL;DR: It is proposed that damaged mitochondria are ubiquitinated and dynamically encased in ER strands, providing platforms for formation of the mitophagosomes.
Journal ArticleDOI
The incredible ULKs
TL;DR: Vertebrate genomes finally encode five closely related kinases, of which UNC-51-like kinase 1 (Ulk1) and Ulk2 are both involved in the regulation of autophagy and further neuron-specific vesicular trafficking processes.
Journal ArticleDOI
The effects and the mechanisms of autophagy on the cancer-associated fibroblasts in cancer.
Yuanliang Yan,Xi Chen,Xiang Wang,Zijin Zhao,Wenfeng Hu,Shuangshuang Zeng,Jie Wei,Xue Yang,Long Qian,Shuyi Zhou,Lun-Quan Sun,Zhicheng Gong,Zhijie Xu +12 more
TL;DR: The mechanism and role of autophagy in cancer-associated fibroblasts is detailed, including the hypoxic-autophagy positive feedback cycle, the metabolic cross-talk between CAFs and tumors induced byAutophagy, CAFs secreted cytokines promote cancer survival by secretory autophile, and the contribution to sensitive treatments as a potential target for cancer treatment is discussed.
References
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LC3, a mammalian homologue of yeast Apg8p, is localized in autophagosome membranes after processing
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Dissection of the Autophagosome Maturation Process by a Novel Reporter Protein, Tandem Fluorescent-Tagged LC3
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mTOR regulation of autophagy
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