Autophagosome formation from membrane compartments enriched in phosphatidylinositol 3-phosphate and dynamically connected to the endoplasmic reticulum

By N. Ktistakis, S. Andrews, Joshua D. Long. Journal of Cell Biology, 2008

1,596 citations recorded by the source corpus.

Autophagy is the engulfment of cytosol and organelles by double-membrane vesicles termed autophagosomes. Autophagosome formation is known to require phosphatidylinositol 3-phosphate (PI(3)P) and occurs near the endoplasmic reticulum (ER), but the exact mechanisms are unknown. We show that double FYVE domain–containing protein 1, a PI(3)P-binding protein with unusual localization on ER and Golgi membranes, translocates in response to amino acid starvation to a punctate compartment partially colocalized with autophagosomal proteins. Translocation is dependent on Vps34 and beclin function. Other PI(3)P-binding probes targeted to the ER show the same starvation-induced translocation that is dependent on PI(3)P formation and recognition. Live imaging experiments show that this punctate compartment forms near Vps34-containing vesicles, is in dynamic equilibrium with the ER, and provides a membrane platform for accumulation of autophagosomal proteins, expansion of autophagosomal membranes, and emergence of fully formed autophagosomes. This PI(3)P-enriched compartment may be involved in autophagosome biogenesis. Its dynamic relationship with the ER is consistent with the idea that the ER may provide important components for autophagosome formation.

Subfields: Cell Biology, Epidemiology, Physiology

View Paper: https://www.semanticscholar.org/paper/b9ad09f43eb8533e2b385a759c7b611c3f4d7f7b

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Citations in the corpus

Fatty acid trafficking in starved cells: regulation by lipid droplet lipolysis, autophagy and mitochondrial fusion dynamics (2015, background): “One is through autophagic digestion of membrane-bound organelles (i.e., the ER) or LDs (Axe et al., 2008; Hayashi-Nishino et al., 2009; Kristensen et al., 2008; Singh et al., 2009a; Ylä-Anttila et al., 2009).”
Eaten alive: a history of macroautophagy (2010, result): “For example, recent studies have suggested that the endoplasmic reticulum membran”
Atg8 family LC3/GABARAP proteins are crucial for autophagosome–lysosome fusion but not autophagosome formation during PINK1/Parkin mitophagy and starvation (2016, background): “PI3P recruits the downstream effectors WIPI1/2 and DFCP1, and together with additional autophagy proteins, including Atg2A/B, Vmp1, and the Atg8s, remodel and expand isolation membranes to form the autophagosome.”
Autophagy and apoptosis dysfunction in neurodegenerative disorders. (2014, neutral): “During further elongation and autophagosome formation around the selected cargo for degradation, recruitment of the membrane from endoplasmic reticulum, mitochondria and at times even nuclear membrane is well documented (Axe et al., 2008; Hailey et al., 2010).”
The origin of the autophagosomal membrane (2010, background): “On starvation, PtdIns(3)P production is induced and occurs ectopically in cellular compartments such as the ER, which is thought to not normally have high levels of PtdIns(3)”
Autophagy, Immunity, and Microbial Adaptations (2009, background): “The origin of the autophagosomal phag-ophore membrane is not known with certainty, but both older and more recent data suggest involvement of the endoplasmic reticulum (ER) (Axe et al., 2008; Matsunaga et al., 2009).”
The emerging mechanisms of isoform-specific PI3K signalling (2010, background): “5a )) seem to form from ER membranes on amino acid starvation of mammalian cell”
Mechanisms of Selective Autophagy (2016, neutral): “This process may occur only at permissive sites that are capable of donating membrane to the process such as ER-related structures in mammalian cells and plants or the PAS in S. cerevisiae [2,119,120].”
A subdomain of the endoplasmic reticulum forms a cradle for autophagosome formation (2009, background): “A recent study using a phosphatidylinositol 3-phosphate (PtdIns(3)P)-binding protein with an ER-targeting signal (DFCP1) showed PtdIns(3)P-enriched subdomains of the ER (omegasomes) that are related to initiation of autophagosome formatio”
Autophagy and the integrated stress response (2010, neutral): “Origin of the Isolation Membrane The isolation membrane can be generated frommultiple sources that include the ER (Axe et al., 2008; Hayashi-Nishino et al., 2009; Yla-Anttila et al., 2009), the outer mitochondrial membrane (Hailey et al., 2010), and the plasma membrane (Ravikumar et al., 2010).”
Monitoring and Measuring Autophagy (2017, background): “The omegasome is characterized by the existence of double-FYVE domain-containing protein 1 (DFCP1), from which the isolation membranes protrude [19] (Figure 1B).”
Two Beclin 1-binding proteins, Atg14L and Rubicon, reciprocally regulate autophagy at different stages (2009, background): “ER has long been considered a candidate for the source of autophagosome membrane and recent paper reported that a specialized domain of ER has an important role in autophagosome formation by recruiting hVps34 (ref”
An Overview of Autophagy: Morphology, Mechanism, and Regulation (2014, background): “Another PtdIns3P-binding protein in mammalian cells is the zinc finger, FYVE domain containing 1 (ZFYVE1/DFCP1), which associates with PtdIns3P-enriched omegasomes (7).”