Journal
JOURNAL OF CELL SCIENCE
Volume 126, Issue 22, Pages 5224-+Publisher
COMPANY BIOLOGISTS LTD
DOI: 10.1242/jcs.132415
Keywords
ULK complex; Autophagy; Imaging; Omegasomes; Phosphatidylinositol 3-phosphate
Categories
Funding
- Biotechnology and Biological Sciences Research Council [BB/H000631/1]
- science policy committee grant from the Babraham Institute, Cambridge [2301-R1600-C0341]
- Grants-in-Aid for Scientific Research [25111005] Funding Source: KAKEN
- BBSRC [BBS/E/B/0000C341, BBS/E/B/0000H103, BBS/E/B/000C0413, BB/K019155/1] Funding Source: UKRI
- Biotechnology and Biological Sciences Research Council [BB/K019155/1, BBS/E/B/00001221, BBS/E/B/0000C221, BB/H000631/1, BBS/E/B/000C0413, BBS/E/B/0000C341, BBS/E/B/0000H103] Funding Source: researchfish
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Induction of autophagy requires the ULK1 protein kinase complex and the Vps34 lipid kinase complex. PtdIns3P synthesised by Vps34 accumulates in omegasomes, membrane extensions of the ER within which some autophagosomes form. The ULK1 complex is thought to target autophagosomes independently of PtdIns3P, and its functional relationship to omegasomes is unclear. Here we show that the ULK1 complex colocalises with omegasomes in a PtdIns3P-dependent way. Live-cell imaging of Atg13 (a ULK1 complex component), omegasomes and LC3 establishes and annotates for the first time a complete sequence of steps leading to autophagosome formation, as follows. Upon starvation, the ULK1 complex forms puncta associated with the ER and sporadically with mitochondria. If PtdIns3P is available, these puncta become omegasomes. Subsequently, the ULK1 complex exits omegasomes and autophagosomes bud off. If PtdIns3P is unavailable, ULK1 puncta are greatly reduced in number and duration. Atg13 contains a region with affinity for acidic phospholipids, required for translocation to punctate structures and autophagy progression.
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