ATG8

Ubiquitin-like modifier involved in cytoplasm to vacuole transport (Cvt) vesicles and autophagosome formation (PubMed:10525546, PubMed:10681575, PubMed:10837468, PubMed:11038174, PubMed:11149920, PubMed:16680092, PubMed:18508918, PubMed:19398890, PubMed:21429936, PubMed:7593182, PubMed:8224160). With ATG4, mediates the delivery of the vesicles and autophagosomes to the vacuole via the microtubule cytoskeleton (PubMed:9649430). Required for selective autophagic degradation of the nucleus (nucleophagy) as well as for mitophagy which contributes to regulate mitochondrial quantity and quality by eliminating the mitochondria to a basal level to fulfill cellular energy requirements and preventing excess ROS production (PubMed:17404498, PubMed:22768199). Participates also in membrane fusion events that take place in the early secretory pathway (PubMed:10837468). Also involved in endoplasmic reticulum-specific autophagic process and is essential for the survival of cells subjected to severe ER stress (PubMed:17132049). The ATG8-PE conjugate mediates tethering between adjacent membranes and stimulates membrane hemifusion, leading to expansion of the autophagosomal membrane during autophagy (PubMed:11100732, PubMed:17632063, PubMed:20855502). Moreover not only conjugation, but also subsequent ATG8-PE deconjugation is an important step required to facilitate multiple events during macroautophagy, and especially for efficient autophagosome biogenesis, the assembly of ATG9-containing tubulovesicular clusters into phagophores/autophagosomes, and for the disassembly of PAS-associated ATG components (PubMed:17632063, PubMed:20855502, PubMed:22622160). Also plays a role in regulation of filamentous growth (PubMed:17700056).

Has a lipidation-independent vacuolar function to facilitate the degradation of vacuolar integral membrane proteins during early-stationary vacuole turnover (EVT) when cells enter stationary phase.

The C-terminal Arg-117 residue of ATG8 is removed by ATG4 to expose Gly-116 at the C-terminus (PubMed:11038174, PubMed:11149920, PubMed:16680092). This Gly-116 forms then a thioester bond with the 'Cys-507' of ATG7 (E1-like activating enzyme) before being transferred to the 'Cys-234' of ATG3 (the specific E2 conjugating enzyme), in order to be finally amidated with phosphatidylethanolamine (PubMed:11100732, PubMed:15277523, PubMed:17632063, PubMed:17699586, PubMed:18725539, PubMed:19285500, PubMed:20428927, PubMed:20615880, PubMed:22539722, PubMed:23064152, PubMed:28330855). This lipid modification anchors ATG8 to membranes and can be reversed by ATG4, releasing soluble ATG8 (PubMed:22240591, PubMed:22622160, PubMed:22652539, PubMed:28330855).

Belongs to the ATG8 family.

• Cytoplasmic vesicle
• Cvt vesicle membrane
• Lipid-anchor
• Cytoplasmic vesicle
• Autophagosome membrane
• Lipid-anchor
• Vacuole membrane
• Peripheral membrane protein
• Mitochondrion membrane
• Peripheral membrane protein
• Membrane-associated through a lipid anchor. This association needs the 2 ubiquitin-like systems required for cytoplasm to vacuole transport and autophagy. ATG18 and ATG21 facilitate the recruitment of ATG8-PE to the site of autophagosome formation and protect it from premature cleavage by ATG4. Localizes to both the isolation membrane (IM) and the vacuole-isolation membrane contact site (VICS) during IM expansion. The IM is a membrane sac generated from the pre-autophagosomal structure that ultimately expands to become a mature autophagosome. Upon starvation, is also recruited to into unique membrane structures near SEC13-containing ER exit sites which lack components of the Golgi apparatus and the endosomes, and which were called a compartments for unconventional protein secretion (CUPS). Associates with mitochondria following nitrogen starvation in a respiratory carbon source (PubMed:30510114).

APG8, AUT7, CVT5, YBL078C, YBL0732, ATG8, Autophagy-related protein 8, Autophagy-related ubiquitin-like modifier ATG8, Cytoplasm to vacuole targeting protein 5

• entrezGene:852200
• swissprot:P38182

Proteins

Neuroscience

13627Da