Autophagy is an essential cellular process, used by cells to degrade damaged and unnecessary cytosolic macromolecules and organelles, for example, proteins. This prevents cell functions and pathways from being damaged or interrupted by aggregates of proteins or non-functioning organelles, a key cause of disease. Autophagy proceeds via a five-step mechanism that starts with the sequestration of cytosolic material by a double-membrane, known as a 'phagophore'. Once the phagophore membrane ends fuse to form a vesicle, the substrate has been fully sequestered. Once sequestration is complete, the autophagosome fuses with a lysosome and up to 40 hydrolytic enzymes digest the autophagosome's cargo.
Autophagy prevents damage occurring to the cell/ tissues by removing harmful molecules and preventing their accumulation. It is extremely prominent in the case of starving cells where nutrients are required to perpetuate cell survival.
One of the key products of autophagy, amino acids, can be used for anabolic processes within the cell.
Autophagy is controlled by mTOR (Mechanistic target of rapamycin), a kinase coded for by the MTOR gene. When mTOR is activated, autophagy is suppressed. mTOR can be suppressed by low amino acid concentrations, allowing autophagy to produce more amino acids.
- ↑ Department of Physiology and Cell Biology, Tokyo Medical and Dental University, Tokyo 113-8519, Japan; Solution Oriented Research for Science and Technology, Japan Science and Technology Agency, Tokyo 102-0075, Japan
- ↑ Lin S., Leng Z., Guo Y., Cai L., Cai Y., Li N., Shang H., Le W., Zhao W., Wu Z. (2015). Suppression of mTOR pathway and induction of autophagy-dependent cell death by cabergoline. Oncotarget, 5744 (Epub ahead of print)
- ↑ Carroll, B., Korolchuk, V., Sarkar, S. (2015). Amino acids and autophagy: cross-talk and co-operation to control cellular homeostasis. Amino Acids, 47(10), pp2065-2088