PtdIns4P restriction by hydrolase SAC1 decides specific fusion of autophagosomes with lysosomes.

PtdIns4P restriction by hydrolase SAC1 decides specific fusion of autophagosomes with lysosomes.
Autophagy. 2020 Jul 21;:
Authors: Zhang H, Zhou J, Xiao P, Lin Y, Gong X, Liu S, Xu Q, Wang M, Ren H, Lu M, Wang Y, Zhu J, Xie Z, Li H, Lu K
Abstract
Biogenesis of autophagosomes is the early step of macroautophagy/autophagy and requires membrane acquisition mainly from ER-Golgi-sourced precursor vesicles. Matured autophagosomes fuse with lysosomes for final degradation. However, how this selective fusion is determined remains elusive. Here, we identified Sac1 by a high throughput screen in Saccharomyces cerevisiae to show it was critical for autophagosome-lysosome fusion through its PtdIns4P phosphatase activity. Sac1 deficiency caused a dramatic increase of PtdIns4P at early Golgi apparatus and abnormal incorporation of PtdIns4P into Atg9 vesicles and autophagosomes, which caused failure to recruit SNARE proteins for autophagosome fusion with vacuoles. Sac1 function in autophagy was highly conserved from yeast to mammalian cells. Our work thus suggested that correct upstream lipid incorporation was important for downstream fusion step of autophagy and that Sac1 played a critical and ancient role in this surveillance of lipid integration.
PMID: 32693712 [PubMed - as supplied by publisher]

Source: Autophagy - July 20, 2020 Category: Cytology Authors: Zhang H, Zhou J, Xiao P, Lin Y, Gong X, Liu S, Xu Q, Wang M, Ren H, Lu M, Wang Y, Zhu J, Xie Z, Li H, Lu K Tags: Autophagy Source Type: research