Dual roles of Atg8-PE deconjugation by Atg4 in autophagy.
Modification of target molecules by ubiquitin or ubiquitin-like (Ubl) proteins is generally reversible. Little is known, however, about the physiological function of the reverse reaction, deconjugation. Atg8 is a unique Ubl protein whose conjugation target is the lipid phosphatidylethanolamine (PE). Atg8 functions in the formation of double-membrane autophagosomes, a central step in the well-conserved intracellular degradation pathway of macroautophagy (hereafter autophagy). Here we show that the deconjugation of Atg8-PE by the cysteine protease Atg4 plays dual roles in the formation of autophagosomes. During the early stage of autophagosome formation, deconjugation releases Atg8 from non-autophagosomal membranes to maintain a proper supply of Atg8. At a later stage, the release of Atg8 from intermediate autophagosomal membranes facilitates the maturation of these structures into fusion-capable autophagosomes. These results provide new insights into the functions of Atg8-PE and its deconjugation.
School of Medicine, Nankai University, Tianjin, China.
Zhong-Qiu
ZQ
Yu
Tao
T
Ni
Bing
B
Hong
Hai-Yan
HY
Wang
Fen-Jun
FJ
Jiang
Shenshen
S
Zou
Yong
Y
Chen
Xi-Long
XL
Zheng
Daniel J
DJ
Klionsky
Yongheng
Y
Liang
Zhiping
Z
Xie
D001343:Autophagy; D000071190:Autophagy-Related Protein 8 Family; D000071183:Autophagy-Related Proteins; D007425:Intracellular Membranes / Q000378:metabolism; D008869:Microtubule-Associated Proteins / Q000378:metabolism*; D008954:Models, Biological; D010588:Phagosomes / Q000378:metabolism; D010714:Phosphatidylethanolamines / Q000378:metabolism*; D012441:Saccharomyces cerevisiae / Q000166:cytology* / Q000378:metabolism*; D029701:Saccharomyces cerevisiae Proteins / Q000378:metabolism*; D014617:Vacuoles / Q000378:metabolism
C113757:ATG8 protein, S cerevisiae; C113755:Atg4 protein, S cerevisiae; D000071190:Autophagy-Related Protein 8 Family; D000071183:Autophagy-Related Proteins; D008869:Microtubule-Associated Proteins; D010714:Phosphatidylethanolamines; D029701:Saccharomyces cerevisiae Proteins; C483858:phosphatidylethanolamine