Beclin 1 |
Member of PtdIns 3-kinase complex, involved in activation of macroautophagy |
[31] |
TSC1 |
Acts as a gtpase-activating protein for Rheb, thus inhibiting TOR |
[32] |
UVRAG |
Member of PtdIns 3-kinase complex, regulates macroautophagy |
[33] |
AEG1 |
Gene encodes oncogenic protein that induces macroautophagy independent of Beclin-1 and PtdIns 3-kinase |
[34] |
Omi/HtrA2 |
Degrades the Bcl-2 family-related protein Ha × −1 to allow macroautophagy induction |
[35] |
Pten |
Dephosphorylates PdtIns(3,4,5)P3 inhibiting PDK1 and PKB/Akt activity |
[36,37] |
Atg14 |
Component of PtdIns 3-kinase complex, targets this complex toward autophagic machinery |
[38] |
Bif-1 |
Interacts with Beclin 1 via UVRAG and is required for macroautophagy |
[39] |
HMGB1 |
Binds beclin-1 to displace Bcl-2 inhibiting apoptosis and promoting macroautophagy |
[40] |
RalB |
Activation of phagophore assembly through ULK1-Beclin1-Vps34 complex assembly and Exo84 interaction |
[41] |
RB1CC1/FIP200 |
Component of Ulk1 complex, required for phagophore formation, phosphorylation of Ulk1/2 |
[42] |
FoxO1 |
Regulates macroautophagy independent of transcriptional control |
[43] |
FoxO3 |
Stimulates macroautophagy through transcriptional control of autophagy genes |
[44] |
PERK/eif2α3K |
Phosphorylated due to ER stress which induces LC3 conversion and macroautophagy |
[45,46] |
Expansion/Closure |
MAPK1 |
MAPK/ERK regulates the maturation of autophagosomes |
[47] |
Atg12 |
Ubiquitin-like protein, conjugates Atg5, member of ATG12–5–16 complex, essential for Map1LC3B/Atg8 activation, involved in mitochondrial homeostasis |
[48,49] |
WIPI1/Atg18 |
Binds PI3P by WD40 β-propeller domain, involved in retrograde movement of Atg9 |
[50,51] |
Atg3 |
E2 ubiquitin ligase, conjugates PE to Map1LC3B after Atg7 processing of c-terminus of cleaved Map1LC3B/Atg8, can be conjugated to Atg12 |
[49,52] |
Atg5 |
Contains ubiquitin-folds, member of ATG12–5–16 complex |
[48] |
Map1LC3b/Atg8 |
Atg8 homolog, involved in autophagosome biogenesis and cargo recruitment to autophagosomes, marker of autophagosomes |
[53–55] |
Atg4a |
Cysteine Protease of Yeast Atg8 homologs, required for Map1LC3B /Atg8 activation, able to deconjugate PE of processed Map1LC3B |
[55,56] |
Rab33B |
Binds Atg16L1, involved in autophagosome maturation by regulation of autophagosome to lysosome fusion, OATL1 binding partner |
[57,58] |
Fusion/Degradation |
FYCO1 |
Rab7 effector, binds Map1LC3B and phosphatidylinositol-3-phosphate, coordinates plus-end directed autophagosome transport |
[26,59] |
Rab7 |
Transport of early to late endosomes, docking protein for amphisome to lysosome fusion |
[26,60–62] |
Rab9 |
Involved in trafficking from late endosomes to the trans-golgi, believed to be a key component of the ATG5/7 alternative macroautophagy pathway |
[60,63] |
VAMP7 |
SNARE protein, required for autophagosome formation, autophagosome maturation via facilitation of autophagosome to lysosome fusion |
[64,65] |
VCP |
AAA+ ATPase, required for autophagosome maturation, mutations to vcp results in accumulation of ubiquitin-containing autophagosomes |
[66,67] |
PSEN1 |
Protease, part of the γ-secretase complex, involved in lysosomal degradation |
[68] |
Mitophagy |
ERK2 |
Localizes to the mitochondria, regulates mitophagy |
[69] |
BNIP3L/NIX |
Bcl2 related, necessary for selective mitochondrial clearance |
[70] |
Pink1 |
Decreased MMP causes altered Pink1 processing, results in spanning of Pink1 across the outer mitochondrialmembrane, recruiting Parkin for mitophagy |
[71] |
PARL |
Mitochondrial protease that regulates PINK1 localization and stability |
[72] |
Chaperone Mediated Autophagy |
Lamp2 |
Lysosomal membrane receptor for chaperone-mediated autophagy allowing translocation of substrates across the lysosomal membrane. |
[73] |
BAG3 |
Directs Hsp70 misfolded protein substrates to dynein targeting them to aggresomes for selective degradation |
[74] |
Hsc70–4 |
Aids in targeting of cytosolic proteins to the lysosome for degradation |
[75] |
hsp90 |
Assists in LAMP-2A stabilization of during its lateral mobility in the lysosomal membrane |
[76] |
Adaptor Proteins |
NBR1 |
Binds ubiquitinated proteins allowing degradation by macroautophagy |
[77,78] |
P62 |
Interacts with Atg8 via its LIR domain, adaptor for degradation of ubiquitin-labeled molecules |
[78,79] |
Autophagy Inhibitors |
mTOR |
Serine/threonine kinase that controls cells growth and metabolism in response to nutrients, growth factors, cellular energy and stress |
[80,81] |
c-Jun |
transcription factor, Inhibits mammalian macroautophagy induced by starvation |
[82] |
p8/Nupr1 |
Inhibits macroautophagy by repressing the transcriptional activity of FoxO3 |
[83] |
PKB/Akt |
Upstream regulator of mtor |
[84] |
PARK7/DJ1 |
Overxpression suppresses macroautophagy through the JNK pathway |
[85] |