UCL logo

UCL Discovery

UCL home » Library Services » Electronic resources » UCL Discovery

Autophagosome formation is initiated at phosphatidylinositol synthase‐enriched ER subdomains

Nishimura, T; Tamura, N; Kono, N; Shimanaka, Y; Arai, H; Yamamoto, H; Mizushima, N; (2017) Autophagosome formation is initiated at phosphatidylinositol synthase‐enriched ER subdomains. The EMBO Journal , 36 (12) pp. 1719-1735. 10.15252/embj.201695189. Green open access

[img]
Preview
Text
75297_2_merged_1490627576.pdf - ["content_typename_Accepted version" not defined]

Download (2MB) | Preview

Abstract

The autophagosome, a double‐membrane structure mediating degradation of cytoplasmic materials by macroautophagy, is formed in close proximity to the endoplasmic reticulum (ER). However, how the ER membrane is involved in autophagy initiation and to which membrane structures the autophagy‐initiation complex is localized have not been fully characterized. Here, we were able to biochemically analyze autophagic intermediate membranes and show that the autophagy‐initiation complex containing ULK and FIP200 first associates with the ER membrane. To further characterize the ER subdomain, we screened phospholipid biosynthetic enzymes and found that the autophagy‐initiation complex localizes to phosphatidylinositol synthase (PIS)‐enriched ER subdomains. Then, the initiation complex translocates to the ATG9A‐positive autophagosome precursors in a PI3P‐dependent manner. Depletion of phosphatidylinositol (PI) by targeting bacterial PI‐specific phospholipase C to the PIS domain impairs recruitment of downstream autophagy factors and autophagosome formation. These findings suggest that the autophagy‐initiation complex, the PIS‐enriched ER subdomain, and ATG9A vesicles together initiate autophagosome formation.

Type: Article
Title: Autophagosome formation is initiated at phosphatidylinositol synthase‐enriched ER subdomains
Open access status: An open access version is available from UCL Discovery
DOI: 10.15252/embj.201695189
Publisher version: http://dx.doi.org/10.15252/embj.201695189
Language: English
Additional information: This version is the author accepted manuscript. For information on re-use, please refer to the publisher’s terms and conditions.
Keywords: ATG9A; autophagy; FIP200; phosphatidylinositol synthase; the ULK complex
UCL classification: UCL > Provost and Vice Provost Offices
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences
UCL > Provost and Vice Provost Offices > UCL SLASH
UCL > Provost and Vice Provost Offices > UCL SLASH > Faculty of Laws
URI: http://discovery.ucl.ac.uk/id/eprint/1571761
Downloads since deposit
108Downloads
Download activity - last month
Download activity - last 12 months
Downloads by country - last 12 months

Archive Staff Only

View Item View Item