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AutophagyAutophagy is a conserved cellular process whereby long-lived and aggregated proteins, as well as excess and damaged organelles are targeted by a double membrane vesicle or autophagosome for elimination. Basal autophagic activity is present in all cells and plays a homeostatic role, allowing the use of basic molecular components (amino acids) as building blocks or energy source. Physiologically, autophagy plays critical roles during organismal development and immune response, by regulating growth and cooperating with the adaptive immune system. In disease states, such as neurodegenerative conditions, inefficient autophagic activity leads to the accumulation of abnormal proteins and formation of intracellular aggregates. Autophagy provides a mechanism to battle and eliminate infectious pathogens. In cancer, autophagy plays a role in promoting or inhibiting tumor growth in a system and stage dependent manner. View Autophagy Pathway Bioinformatics Tool
Explore Methods to Measure Autophagy Types of AutophagyMacroautophagy:Macroautophagy involves the sequestering of cytosolic components within a double membrane organelle called the autophagosome, transport to the lysosome, and the subsequent cargo degradation. Hereafter, macroautophagy is referred to as autophagy.
Microautophagy:Microautophagy is the process where lysosomes directly engulf cytosolic components via lysosomal membrane invagination or protrusion without prior formation of an autophagosome. The vacuole containing cargo separates from the membrane, becoming internalized within the lysosome as a microautophagic body. Similar to what is observed in macroautophagy, the microautophagic body is lysed and the contents are broken down by vacuolar hydrolases into macromolecules that can be recycled. View Microautophagy Products. Chaperone-Mediated Autophagy:Chaperone mediated autophagy (CMA) is unique from the other two types of autophagy in that the process does not involve generation of autophagic bodies. Similar to microautophagy, CMA also occurs independent of the autophagosome, however, CMA does not involve lysosomal invagination. Instead, chaperone proteins (e.g., heat shock cognate 70 protein; HSC70) recognize cytosolic cargo destined by degradation by their consensus sequence known as the KFERQ-like motif. This chaperone-cargo complex associates with membrane-bound lysosomal-associated membrane protein-2A (LAMP-2A), resulting in the translocation of the unfolded cytosolic protein into the lysosome. View Chaperone-Mediated Autophagy Products. View Interactive Autophagy Pathway ReferencesBento, C. F., Renna, M., Ghislat, G., Puri, C., Ashkenazi, A., Vicinanza, M., Menzies, F. M., & Rubinsztein, D. C. (2016). Mammalian Autophagy: How Does It Work?. Annual review of biochemistry. https://doi.org/10.1146/annurev-biochem-060815-014556
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