Atg8, a ubiquitin-like protein required for autophagosome formation, mediates membrane tethering and hemifusion.

By H. Nakatogawa, Yoshinobu Ichimura, Y. Ohsumi. Cell, 2007

1,228 citations recorded by the source corpus.

Autophagy involves de novo formation of double membrane-bound structures called autophagosomes, which engulf material to be degraded in lytic compartments. Atg8 is a ubiquitin-like protein required for this process in Saccharomyces cerevisiae that can be conjugated to the lipid phosphatidylethanolamine by a ubiquitin-like system. Here, we show using an in vitro system that Atg8 mediates the tethering and hemifusion of membranes, which are evoked by the lipidation of the protein and reversibly modulated by the deconjugation enzyme Atg4. Mutational analyses suggest that membrane tethering and hemifusion observed in vitro represent an authentic function of Atg8 in autophagosome formation in vivo. In addition, electron microscopic analyses indicate that these functions of Atg8 are involved in the expansion of autophagosomal membranes. Our results provide further insights into the mechanisms underlying the unique membrane dynamics of autophagy and also indicate the functional versatility of ubiquitin-like proteins.

Subfields: Cell Biology, Epidemiology, Parasitology

View Paper: https://www.semanticscholar.org/paper/8aa78c46b5fd674eb0682d0f18e52d020c5de90d

How researchers see this paper

The researchers whose trusted networks rank it highest, strongest advocate first. Every researcher gets a different order.

In Cell Biology

1. D. Klionsky
2. N. Mizushima
3. Zhifen Yang
4. T. Yoshimori
5. Yongqiang Chen
6. I. Slaninová
7. P. Codogno
8. Ivan Dikic

In Epidemiology

1. D. Klionsky
2. N. Mizushima
3. Beth Levine
4. I. Slaninová
5. Zhifen Yang
6. Guido Kroemer
7. R. Youle
8. T. Yoshimori

In Parasitology

1. D. Klionsky
2. N. Mizushima
3. Zhifen Yang
4. Yongqiang Chen
5. T. Yoshimori
6. Ivan Dikic
7. P. Codogno
8. Beth Levine

Citations in the corpus

• The Atg16L complex specifies the site of LC3 lipidation for membrane biogenesis in autophagy. (2008, background): “Recently, Nakatogawa et al. (2007) showed that Atg8-PE is potent in causing the hemifusion of vesicles/ micelles in vitro, and this property may be related to the membrane elongation step of autophagosome formation.”
• Emerging regulation and functions of autophagy (2013, background): “The role of LC3-II and other members of the Atg8 protein family in these processes probably relies on their capacities in mediating tethering or fusion of vesicular structures 56, 57 and/or binding the cytoskeleton 58 .”
• Molecular mechanisms and physiological functions of mitophagy (2021, neutral): “Although damaged mitochondria are properly sequestered by autophagosomal membranes in cells lacking all Atg8 family proteins, the size of autophagosomes is much smaller than that in wild-type cells (Nakatogawa et al , 2007; Weid-berg et al , 2010).”
• Deacetylation of nuclear LC3 drives autophagy initiation under starvation. (2015, background): “Deacetylation of LC3 Is Essential for LC3-Atg7 Interaction Conjugation of LC3 to PE requires LC3 to interact sequentially with Atg7 and Atg3 (Ichimura et al., 2000; Nakatogawa et al., 2007).”
• The Atg8 and Atg12 ubiquitin‐like conjugation systems in macroautophagy (2008, background): “…cytosolic components or organelles. recently, nakatogawa and colleagues reported that atg8–pE can mediate membrane tethering and hemifusion in vitro (nakatogawa et al, 2007), although it is unclear how membrane fusion in vivo occurs only on the edge of the expanding phagophore if atg8 is…”
• Mechanisms of mitophagy (2011, background): “LC3 (and Atg8) is an ubiquitin-like protein that is covalently attached to phosphatidylethanolamine during autophagosome biogenesis, which allows it to integrate into, and sculpt, the growing isolation membran”
• An Overview of the Molecular Mechanism of Autophagy (2009, background): “Atg8 is also suggested to act during the expansion of the autophagosomal membrane by mediating membrane tethering and hemifusion (Nakatogawa et al. 2007), although the physiological significance of this activity is not yet known.”
• Mitochondria supply membranes for autophagosome biogenesis during starvation (2010, background): “LC3 can catalyze homotypic membrane fusion in an in vitro system (Nakatogawa et al., 2007).”
• Atg8 family LC3/GABARAP proteins are crucial for autophagosome–lysosome fusion but not autophagosome formation during PINK1/Parkin mitophagy and starvation (2016, background): “Consistent with reported roles for Atg8s in expanding autophagosomal membranes (Nakatogawa et al., 2007; Weidberg et al., 2010), we observed smaller autophagosomes in hexa KO cells (Fig.”
• Autophagy: process and function. (2007, background): “Atg8 mediates tethering and hemifusion of liposomes containing Atg8-PE in an in vitro system (Nakatogawa et al. 2007).”
• mTOR regulation of autophagy (2010, background): “plexes to autophagosome given their implicated functions in vesicle transport and fusion [79,80].”
• Ubiquitination and selective autophagy (2012, background): “In the conjugated form, LC3 seems to be indispensable for hemifusion of lipid membranes, thereby driving expansion of the autophagosome.(48) Furthermore, LC3 may also control the size of autophagosomes.”