An Atg4B mutant hampers the lipidation of LC3 paralogues and causes defects in autophagosome closure

Naonobu Fujita, Mitsuko Hayashi-Nishino, Hiromi Fukumoto, Hiroko Omori, Akitsugu Yamamoto, Takeshi Noda, Tamotsu Yoshimori

研究成果: Article査読

361 被引用数 (Scopus)

抄録

In the process of autophagy, a ubiquitin-like molecule, LC3/Atg8, is conjugated to phosphatidylethanolamine (PE) and associates with forming autophagosomes. In mammalian cells, the existence of multiple Atg8 homologues (referred to as LC3 paralogues) has hampered genetic analysis of the lipidation of LC3 paralogues. Here, we show that overexpression of an inactive mutant of Atg4B, a protease that processes pro-LC3 paralogues, inhibits autophagic degradation and lipidation of LC3 paralogues. Inhibition was caused by sequestration of free LC3 paralogues in stable complexes with the Atg4B mutant. In mutant overexpressing cells, Atg5- and ULK1-positive intermediate autophagic structures accumulated. The length of these membrane structures was comparable to that in control cells; however, a significant number were not closed. These results show that the lipidation of LC3 paralogues is involved in the completion of autophagosome formation in mammalian cells. This study also provides a powerful tool for a wide variety of studies of autophagy in the future.

本文言語English
ページ(範囲)4651-4659
ページ数9
ジャーナルMolecular biology of the cell
19
11
DOI
出版ステータスPublished - 2008 11
外部発表はい

ASJC Scopus subject areas

  • 分子生物学
  • 細胞生物学

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