Review Article

Autophagy and Redox Homeostasis in Parkinson’s: A Crucial Balancing Act

Table 1

Key proteins involved in the various stages of autophagy and their general roles.

ProteinFunctionsStages

ATG proteins
ULK1/2Serine/threonine kinase that forms complexes with ATG13, FIP200, and ATG101, involved in ATG9 recruitment and the activation of the PI3KC3 complex.Initiation/nucleation
ATG2A/BATG2A interacts with WIPI4, tethering the omegasome to the ER. ATG2-GABARAP interaction is critical for autophagosome closure.Elongation and maturation (closure)
ATG3E2-like enzyme coordinating ATG8 conjugation to PE.Elongation
ATG4A/B/C/DCysteine protease that activates (priming) and recycles (delipidation) ATG8s by cleavage of pro-ATG8 and ATG8-PE, respectively for autophagosome formation and possibly maturation).Elongation
ATG5Conjugates to ATG12, and acts as an E3-like enzyme for ATG8 conjugation to PE.Elongation
BECLIN1Regulatory subunit of the PI3KC3 Complex I.Initiation/nucleation
ATG7E1-like enzyme. Coordinates conjugation of ATG12 to ATG5, and ATG8 conjugation to PE.Elongation
LC3A/B/CConjugates 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
GABARAPsParallel functions with LC3A/BC, although GABARAPs seem to be particularly important for autophagosome maturation.Elongation, maturation, and fusion
ATG9Transmembrane protein involved in delivery of membrane to the PAS/autophagosome assembly site.Initiation/nucleation
ATG10E2-like enzyme. Coordinates the conjugation of ATG12 to ATG5.Elongation
ATG12Conjugates to ATG5, forming the E3-like enzyme for conjugation of ATG8 to PE.Elongation
ATG13Regulatory subunit of the ULK1/2 complex.Initiation/nucleation
ATG14L1Core component of PI3KC3 Complex I, required for ER localization. Stabilises SNARE complexes for autophagosome-lysosome fusion.Initiation/nucleation and fusion
ATG16L1Forms a complex with ATG12-ATG5. Provides E3-like activity for conjugation of ATG8 to PE.Elongation
ATG17Scaffolding protein for the recruitment of ATG9 vesicles. ESCRT recruitment.Initiation/nucleation and maturation (closure)
ATG101Core component of the ULK1 complex.Initiation/nucleation
FIP200Core component of the ULK1 complex.Initiation/nucleation
WIPI1/2/3/4PI3P effector protein. WIPI2 recruits the ATG12-ATG5-ATG16L1 complex at the phagophore.Elongation
Non-ATG proteins
ALFYPI3P effector protein involved in the degradation of protein aggregates.Elongation
AMBRA1Regulator of the PI3KC3 complex.Initiation/nucleation
AMPKSerine/threonine kinase. Autophagy activator via phosphorylation of ULK1 and inhibition of mTOR.Initiation/nucleation
BassonScaffold protein in neuronal active zone. Involved in ATG5 sequestration.Initiation
DFCP1PI3P effector protein. Efficient omegasome marker.Elongation
Endophilin AAdaptor protein involved in synaptic vesicle recycling and ATG3 recruitment.Initiation
ESCRTMembrane fission.Maturation (closure)
FBXO7E3-like enzyme involved in mitochondrial Parkin recruitment.Initiation/nucleation (mitophagy)
FYCO1Rab7 effector. Binds to PI3P and LC3. Mediates anterograde kinesin-driven transport.Maturation (trafficking)
mTORC1Serine/threonine kinase complex. Autophagy inhibitor via phosphorylation of ULK1.Initiation/nucleation
ParkinE3-like enzyme. Ubiquitination of mitochondrial surface proteins.Initiation/nucleation (mitophagy)
PEX5Protein 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)
PiccoloScaffold protein in the neuronal active zone. Involved in ATG5 sequestration.Initiation
PINK1Serine/threonine kinase. Drives the phosphorylation of ubiquitin and Parkin, for robust mitochondrial Parkin recruitment.Initiation/nucleation (mitophagy)
RAB7Autophagosome trafficking (interaction with FYCO1 or RILP) and autophagosome-lysosome fusion (interaction with PLEKHM1).Maturation and fusion
SynaptojaninEnzyme involved in neuronal membrane trafficking. Promotes autophagosome maturation.Maturation
SNAREsOn the autophagosome, STX17 and SNAP29, and on the lysosome, VAMP7 or VAMP8, mediates membrane fusion supported by HOPS and ATG14L1.Fusion
TBK1Serine/threonine kinase. Increases the binding affinity of autophagy receptorsElongation
UVRAGCore component of PI3KC3 Complex II.Maturation and fusion
VPS15Adaptor protein and core component of PI3KC3 complex.Initiation/nucleation
VPS34Catalytic subunit of the PI3KC3 complex.Initiation/nucleation
Autophagy receptors
P62, NDP52, OPTN, NRB1, TAX1BP1, NIX, FUNDC1, CCPG1, RTN3, SEC62, ATL3, CALCOCO1, FAM134B, TEX264Binding to ubiquitinated substrates and ATG8s.Cargo recruitment to the phagophore