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

Autophagy
Hongjun ZhangKefeng Lu

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.Abbreviations: Ape1: aminopeptidase Ι; ATG: autophagy related; EBSS: Earle's balanced salt solution; ER: endoplasmic reticulum; ERGIC: Golgi apparatus and ER-Golgi intermediate compartment; HOPS: homotypic fusion and protein sorting complex...Continue Reading

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Citations

May 11, 2021·Autophagy·Mariya LichevaFulvio Reggiori
Aug 28, 2021·Cells·Nica BorgeseFrancesca Navone
Oct 14, 2021·Bioscience, Biotechnology, and Biochemistry·Junlin Chen, Manabu Arioka

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Methods Mentioned

BETA
transfections
fluorescence microscopy
transmission electron microscopy
transfection
GTPase

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