The mammalian counterparts of this complex include Beclin 1 (BECN1), ATG14L (Barkor), AMBRA1
, hVps34, and p150 (13).
Positive regulators of autophagy include VPS34, VPS15, UVRAG, ATG14, AMBRA1
, HMGB1, and Bif-1, with AMBRA1
promoting autophagy as well as being involved in the nutrient-dependent localization of Beclin-1.
Mori et al., "AMBRA1
, a novel alphasynuclein-binding protein, is implicated in the pathogenesis of multiple system atrophy," Brain Pathology, vol.
For example, the ULK1-ATG13-FIP200-ATG101 complex is responsible for the induction of autophagy [16, 17], the class III phosphatidylinositol (PtdIns) 3-kinase complex (BECN1, ATG14/ATG14L, VPS15, VPS34, and AMBRA1
) is responsible for the initiation of the autophagosome [18, 19], and the ATG12-5-16 and LC3-II are responsible for the formation of autophagosome [20-22].
Nazio et al., "The dynamic interaction of AMBRA1
with the dynein motor complex regulates mammalian autophagy," Journal of Cell Biology, vol.
Yet, beclin1, Ambra1
, and Rb1cc1/FIP200 knockout mice are unable to produce homozygous offspring due to early embryonic lethality, suggesting that these genes have other important functions during development in addition to their participation in autophagy [5, 7].
Antonioli et al., "mTOR inhibits autophagy by controlling ULK1 ubiquitylation, self-association and function through AMBRA1
and TRAF6," Nature Cell Biology, vol.
Nazio, F., Cecconi, F., 2013, mTOR AMBRA1
, and autophagy: an intricate relationship.
PabloDe, "Atg5 and Ambra1
differentially modulate neurogenesis in neural stem cells," Autophagy, vol.
In addition, the PINK1-Parkin complex can also directly interact with Beclin-1 in the class III phosphoinositide 3-kinase (PI3K) complex, or indirectly with the PI3K complex via AMBRA1
, to initiate autophagosome membrane biogenesis around the damaged organelle [71, 72].
The analysis of specific gene expression profiling by array (Affymetrix Human Gene 1.0 ST Array) of DLP1, GDAP1, MIEF1, MFN2, OPA1, STOML2, Optineurin, ATG5, ATG12, Beclin1, PI3K class III, ULK1, AMBRA1
, BNIP3, BNIP3L, FUNDC1, VDAC1, and VPC/ p97 of human brain samples was retrieved from Berchtold data set .
Phagophore nucleation requires the formation of a complex consisting of the vacuolar protein sorting (VPS) 34, VPS15, Beclin1, and the activating autophagy/beclin-1 regulator 1 (AMBRA1
) ; in this process, B-cell lymphoma 2 (BCL-2) inhibits autophagy by binding Beclin1, while BCL-2-homology 3 (BH3-only) activates the VPS34 complex by displacement of the BCL-2 protein .