Autophagy is the process by which cells consume their own organelles, proteins and other molecules.
Types
There are three main types of autophagy:
- Macroautophagy, where a large portion of cytosol and organelles are enveloped in the autophagosome.
- Microautophagy, where the lysosome directly phagocytoses a molecule.
- Chaperone-assisted autophagy, where molecules are targeted by chaperone proteins to target them for phagocytosis.
Pathogenesis
The main trigger for autophagy is nutrient depletion or depletion of growth factors. These triggers result in the formation of the ULK1 initiation complex. The initiation complex drives the formation of an isolation membrane from the endoplasmic reticulum. mTOR serves to inhibit ULK1 during amino acid sufficiency. With inadequate amino acids in nutrient depletion, mTOR’s activity decreases, allowing the activity of ULK1.
After the isolation membrane is formed, Beclin 1-VPS34 complex helps the isolation membrane target its target. ATG9 and VMP1 recruits lipids to the isolation membrane to allow it to extend around its target and the surrounding cytosol. The ATG12 system and the LC3 system, two ubiquitin-like protein conjugation systems, coordinate the elongation and closure of the membrane around the target, forming the autophagosome. SNARE-like proteins are used to dock and fuse the lysosome to the autophagosome to complete the autophagy process.
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