Table 2 of
Brennan, Mol Vis 2012; 18:1773-1786.
Table 2. Identified autophagy genes and their functions.
Induction | Role in Autophagy | Reference |
---|---|---|
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] |