scholarly journals Atlastin 2/3 regulate ER targeting of the ULK1 complex to initiate autophagy

2021 ◽  
Vol 220 (7) ◽  
Author(s):  
Nan Liu ◽  
Hongyu Zhao ◽  
Yan G. Zhao ◽  
Junjie Hu ◽  
Hong Zhang
Keyword(s):  
Transmembrane Proteins ◽  
Autophagosome Formation ◽  
Subsequent Formation ◽  
Dynamic Assembly ◽  
Er Targeting

Dynamic targeting of the ULK1 complex to the ER is crucial for initiating autophagosome formation and for subsequent formation of ER–isolation membrane (IM; autophagosomal precursor) contact during IM expansion. Little is known about how the ULK1 complex, which comprises FIP200, ULK1, ATG13, and ATG101 and does not exist as a constitutively coassembled complex, is recruited and stabilized on the ER. Here, we demonstrate that the ER-localized transmembrane proteins Atlastin 2 and 3 (ATL2/3) contribute to recruitment and stabilization of ULK1 and ATG101 at the FIP200-ATG13–specified autophagosome formation sites on the ER. In ATL2/3 KO cells, formation of FIP200 and ATG13 puncta is unaffected, while targeting of ULK1 and ATG101 is severely impaired. Consequently, IM initiation is compromised and slowed. ATL2/3 directly interact with ULK1 and ATG13 and facilitate the ATG13-mediated recruitment/stabilization of ULK1 and ATG101. ATL2/3 also participate in forming ER–IM tethering complexes. Our study provides insights into the dynamic assembly of the ULK1 complex on the ER for autophagosome formation.

scholarly journals Autophagy requires endoplasmic reticulum targeting of the PI3-kinase complex via Atg14L

2010 ◽  
Vol 190 (4) ◽  
pp. 511-521 ◽  
Author(s):  
Kohichi Matsunaga ◽  
Eiji Morita ◽  
Tatsuya Saitoh ◽  
Shizuo Akira ◽  
Nicholas T. Ktistakis ◽  
...  
Keyword(s):  
Endoplasmic Reticulum ◽  
Mammalian Cells ◽  
Embryonic Stem ◽  
Pi3 Kinase ◽  
Class Iii ◽  
Autophagosome Formation ◽  
Membranous Structure ◽  
Er Targeting ◽  
Endoplasmic Reticulum Targeting ◽  
Phosphatidylinositol 3

Autophagy is a catabolic process that allows cells to digest their cytoplasmic constituents via autophagosome formation and lysosomal degradation. Recently, an autophagy-specific phosphatidylinositol 3-kinase (PI3-kinase) complex, consisting of hVps34, hVps15, Beclin-1, and Atg14L, has been identified in mammalian cells. Atg14L is specific to this autophagy complex and localizes to the endoplasmic reticulum (ER). Knockdown of Atg14L leads to the disappearance of the DFCP1-positive omegasome, which is a membranous structure closely associated with both the autophagosome and the ER. A point mutation in Atg14L resulting in defective ER localization was also defective in the induction of autophagy. The addition of the ER-targeting motif of DFCP1 to this mutant fully complemented the autophagic defect in Atg14L knockout embryonic stem cells. Thus, Atg14L recruits a subset of class III PI3-kinase to the ER, where otherwise phosphatidylinositol 3-phosphate (PI3P) is essentially absent. The Atg14L-dependent appearance of PI3P in the ER makes this organelle the platform for autophagosome formation.

scholarly journals The GET pathway safeguards against non-imported mitochondrial protein stress

2020 ◽  
Author(s):  
Tianyao Xiao ◽  
Viplendra P.S. Shakya ◽  
Adam L. Hughes
Keyword(s):  
Endoplasmic Reticulum ◽  
Mitochondrial Protein ◽  
Transmembrane Proteins ◽  
Mitochondrial Proteins ◽  
Mitochondrial Import ◽  
Cellular Toxicity ◽  
Precursor Proteins ◽  
Dependent Protein ◽  
Er Targeting ◽  
Get Complex

SUMMARYDeficiencies in mitochondrial import cause the toxic accumulation of non-imported mitochondrial precursor proteins. Numerous fates for non-imported mitochondrial precursors have been identified, including proteasomal destruction, deposition into protein aggregates, and mis-targeting to other organelles. Amongst organelles, the endoplasmic reticulum (ER) has emerged as a key destination for non-imported mitochondrial proteins, but how ER-targeting of these proteins is achieved remains unclear. Here, we show that the guided entry of tail-anchored proteins (GET) complex is required for ER-targeting of endogenous mitochondrial multi-transmembrane proteins. Without a functional GET pathway, non-imported mitochondrial proteins destined for the ER are alternatively sequestered into Hsp42-dependent protein foci. The ER targeting of non-imported mitochondrial proteins by the GET complex prevents cellular toxicity and facilitates re-import of mitochondrial proteins from the ER via the recently identified ER-SURF pathway. Overall, this study outlines an important and unconventional role for the GET complex in mitigating stress associated with non-imported mitochondrial proteins.

Features of the development of an unmanned rocket-culture technology in the first half of the twentieth century

2018 ◽  
pp. 135-144
Author(s):  
O. O. Gubka
Keyword(s):  
Twentieth Century ◽  
Subsequent Formation ◽  
Technical Schools ◽  
Space Industry ◽  
The World ◽  
Culture Technology

The features of unmanned rocket and space engineering´s development in the USSR and in the world in the first half of the XX century were considered in the article. They defined subsequent formation of scientific and technical schools in the rocket and space industry.

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