Table 1.
Key proteins involved in the various stages of autophagy and their general roles.
| Protein | Functions | Stages |
|---|---|---|
| ATG proteins | ||
| ULK1/2 | Serine/threonine kinase that forms complexes with ATG13, FIP200, and ATG101, involved in ATG9 recruitment and the activation of the PI3KC3 complex. | Initiation/nucleation |
| ATG2A/B | ATG2A interacts with WIPI4, tethering the omegasome to the ER. ATG2-GABARAP interaction is critical for autophagosome closure. | Elongation and maturation (closure) |
| ATG3 | E2-like enzyme coordinating ATG8 conjugation to PE. | Elongation |
| ATG4A/B/C/D | Cysteine protease that activates (priming) and recycles (delipidation) ATG8s by cleavage of pro-ATG8 and ATG8-PE, respectively for autophagosome formation and possibly maturation). | Elongation |
| ATG5 | Conjugates to ATG12, and acts as an E3-like enzyme for ATG8 conjugation to PE. | Elongation |
| BECLIN1 | Regulatory subunit of the PI3KC3 Complex I. | Initiation/nucleation |
| ATG7 | E1-like enzyme. Coordinates conjugation of ATG12 to ATG5, and ATG8 conjugation to PE. | Elongation |
| LC3A/B/C | Conjugates to the lipid, PE. Involved in membrane tethering, and phagophore expansion and closure. Coordinates cargo recruitment by binding to autophagy receptors. Binding to FYCO1 promotes microtubule-based transport and autophagosome maturation. Regulates autophagosome-lysosome fusion (binding to PLEKHM1 and HOPS). | Elongation, maturation, and fusion |
| GABARAPs | Parallel functions with LC3A/BC, although GABARAPs seem to be particularly important for autophagosome maturation. | Elongation, maturation, and fusion |
| ATG9 | Transmembrane protein involved in delivery of membrane to the PAS/autophagosome assembly site. | Initiation/nucleation |
| ATG10 | E2-like enzyme. Coordinates the conjugation of ATG12 to ATG5. | Elongation |
| ATG12 | Conjugates to ATG5, forming the E3-like enzyme for conjugation of ATG8 to PE. | Elongation |
| ATG13 | Regulatory subunit of the ULK1/2 complex. | Initiation/nucleation |
| ATG14L1 | Core component of PI3KC3 Complex I, required for ER localization. Stabilises SNARE complexes for autophagosome-lysosome fusion. | Initiation/nucleation and fusion |
| ATG16L1 | Forms a complex with ATG12-ATG5. Provides E3-like activity for conjugation of ATG8 to PE. | Elongation |
| ATG17 | Scaffolding protein for the recruitment of ATG9 vesicles. ESCRT recruitment. | Initiation/nucleation and maturation (closure) |
| ATG101 | Core component of the ULK1 complex. | Initiation/nucleation |
| FIP200 | Core component of the ULK1 complex. | Initiation/nucleation |
| WIPI1/2/3/4 | PI3P effector protein. WIPI2 recruits the ATG12-ATG5-ATG16L1 complex at the phagophore. | Elongation |
| Non-ATG proteins | ||
| ALFY | PI3P effector protein involved in the degradation of protein aggregates. | Elongation |
| AMBRA1 | Regulator of the PI3KC3 complex. | Initiation/nucleation |
| AMPK | Serine/threonine kinase. Autophagy activator via phosphorylation of ULK1 and inhibition of mTOR. | Initiation/nucleation |
| Basson | Scaffold protein in neuronal active zone. Involved in ATG5 sequestration. | Initiation |
| DFCP1 | PI3P effector protein. Efficient omegasome marker. | Elongation |
| Endophilin A | Adaptor protein involved in synaptic vesicle recycling and ATG3 recruitment. | Initiation |
| ESCRT | Membrane fission. | Maturation (closure) |
| FBXO7 | E3-like enzyme involved in mitochondrial Parkin recruitment. | Initiation/nucleation (mitophagy) |
| FYCO1 | Rab7 effector. Binds to PI3P and LC3. Mediates anterograde kinesin-driven transport. | Maturation (trafficking) |
| mTORC1 | Serine/threonine kinase complex. Autophagy inhibitor via phosphorylation of ULK1. | Initiation/nucleation |
| Parkin | E3-like enzyme. Ubiquitination of mitochondrial surface proteins. | Initiation/nucleation (mitophagy) |
| PEX5 | Protein family involved in peroxisome biogenesis and pexophagy. PEX5 is ubiquitinated by the PEX2-PEX10-PEX12 E3-like complex and it is recognised by cargo receptors. | Initiation (pexophagy) |
| Piccolo | Scaffold protein in the neuronal active zone. Involved in ATG5 sequestration. | Initiation |
| PINK1 | Serine/threonine kinase. Drives the phosphorylation of ubiquitin and Parkin, for robust mitochondrial Parkin recruitment. | Initiation/nucleation (mitophagy) |
| RAB7 | Autophagosome trafficking (interaction with FYCO1 or RILP) and autophagosome-lysosome fusion (interaction with PLEKHM1). | Maturation and fusion |
| Synaptojanin | Enzyme involved in neuronal membrane trafficking. Promotes autophagosome maturation. | Maturation |
| SNAREs | On the autophagosome, STX17 and SNAP29, and on the lysosome, VAMP7 or VAMP8, mediates membrane fusion supported by HOPS and ATG14L1. | Fusion |
| TBK1 | Serine/threonine kinase. Increases the binding affinity of autophagy receptors | Elongation |
| UVRAG | Core component of PI3KC3 Complex II. | Maturation and fusion |
| VPS15 | Adaptor protein and core component of PI3KC3 complex. | Initiation/nucleation |
| VPS34 | Catalytic subunit of the PI3KC3 complex. | Initiation/nucleation |
| Autophagy receptors | ||
| P62, NDP52, OPTN, NRB1, TAX1BP1, NIX, FUNDC1, CCPG1, RTN3, SEC62, ATL3, CALCOCO1, FAM134B, TEX264 | Binding to ubiquitinated substrates and ATG8s. | Cargo recruitment to the phagophore |