Autophagy, or autophagocytosis, is a catabolic process involving the degradation of a cell's own components through the lysosomal machinery.
It is the major mechanism by which a starving cell reallocates nutrients from unnecessary processes to more-essential processes or from damaged to healthy parts of the cell (competition).
The same mechanism is used against pathogenes (bacteria and virus), other suffering cells, misfolded or no longer useful proteins, extracellular proteins like serum or extracellular matrix proteins, all used as nutriens.
MHC I is involved in the recognition of proteins to be digested. ??????
It is an active process strongly dependent on the cell capability to acidify lysosomes.
Wikigenes Autophagy
Steps details
INDUCTION:
ATG1/Ulk1 is dowsntream of mTOR and is involved in autophagy induction.
mTOR patway is down-regulated by AMPK (activated by AMP, Metformin, AICAR)
AMPK activation depends on:
- AMP
- Metformin
- AICAR
- purine biosynthesis
- histidine catabolism
NUCLEATION Autophagosome nucleation is driven by phosphatidylinositol (PI) phosphorylation.
- the process is mediated by a lipid kinase signaling complex: Beclin 1, Vps15, Vps34 (Ambra1 favors Vps34/Beclin 1 interaction)
- UVRAG and Bif-1 have been described as additional Beclin 1 complex regulators.
- Beclin 1 proautophagic roles are inhibited by its binding to Bcl2 and/or Bcl-XL, which act in the crosstalk between autophagy and apoptosis.
- APOPTOSIS Bcl2-like pro-apoptotic and antiapoptotic proteins regulate cytochrome c release from mitochondria. Cytosolic cytochrome c binds Apaf1 and induces the recruitment of the initiator caspase 9 (Casp9) on the active apoptosome. The active apoptosome, in turn, activates caspase 3 (Casp3), which mediates cell destruction.
Autophagy at Kegg Pathways
Atg5: more than an autophagy factor 2006
Self-eating and self-killing: crosstalk between autophagy and apoptosis 2007
ATG7 or ATG5
1. FUNCTION: Functions as an E1 enzyme essential for multisubstrates such as GABARAPL1 and ATG12. Forms intermediate conjugates with GABARAPL1 (GABARAPL2, GABARAP or MAP1ALC3). Formation of the final GABARAPL1-PE conjugate is essential for autophagy (By similarity).
2. SUBUNIT: Homodimer (By similarity). Interacts with ATG3 and ATG12. The complex, composed of ATG3 and ATG7, plays a role in the conjugation of ATG12 to ATG5.
3. SUBCELLULAR LOCATION: Cytoplasm (Probable).
4. ALTERNATIVE PRODUCTS: Event=Alternative splicing; Named isoforms=2; Name=1; IsoId=O95352-1; Sequence=Displayed; Name=2; IsoId=O95352-2; Sequence=VSP_013205;
5. TISSUE SPECIFICITY: Widely expressed, especially in kidney, liver, lymph nodes and bone marrow.
6. DOMAIN: The C-terminal part of the protein is essential for the dimerization and interaction with ATG3 and ATG12 (By similarity).
7. SIMILARITY: Belongs to the ATG7 family.
Gaba R increases Cl- influx. What about CFTR?