Autophagy L2

• Macroautophagy is a process whereby cells sequester large portions of their own cytoplasm to form an autophagosome, which then fuses with a lysosome to become an autolysosome.
• Macroautophagy has a lipidated enzyme embedded in the membrane, LC3-II & is a marker for autophagy.
• Microautophagy is where there is an invagination of the lysosme and material enters
• Chaperone mediated autophagy is autophagy of single proteins targetted to the lysosme instead of the proteosome.

  Substrate binds & sends to LAMP-2A protein unfolds & degrades
• UPS where individual proteins, short-lived are ubiquinated and degraded by the 26S proteasome.

  Substrate binds to E3 and transfered to E2 and gets ubiquitinated, chaperone binds to the ubiquitin proteosome region, delivers the polyubiquitin added substrate to the proteosome, goes in unfolds and degrades self.
• UPS does not work when there is aggregated proteins, difficult to degrade
• Autophagy only works for large protein aggregates, cargo engulfed and sent to lysosome for degraded
• Baseline autophagy?


  is random, is regular housekeeping autophagy, randomly appears and engulfs stuff in the vicinity of the autophagosome

  initated for the ER and cytoskel network

  redundancy present to prevent consumption of important stuff.
• Selective autophagy?


  Specific degradation of targeted cellular components to recycle stuff to provide new macromolecules.

  Induced by cellular stresses (hypoxia/ros/infection/starvation) and occurs higher level than basal
• Sources of membrane for autophagosome

  Endoplasmic reticulum (ER) proteins and the mitochondrion
• Mitochondrion membrane sourced by phosphotidyl serine converted to phosphotidylethanolamine forms an organelle contact point and gets covalently attached to LC3, and forms a phagophore.

  1. PS in the mitochondrial membrane is converted to phosphatidylethanolamine (PE).
  2. LC3-I is lipidated by PE to form LC3-II.
  3. LC3-II integrates into the phagophore membrane.
  4. The phagophore closes, forming an autophagosome, which fuses with a lysosome for degradation.
• ER membrane is sourced, uses lots of protein complexes & membrane proteins to induce membrane curvature allowing the ER to curl back upon itself
• effect of using membrane sources?

  renewal of the cells
• sources of membrane?


  any organelle with a membrane really that needs to be recycled
• double membrane is because of the fusion with the endosome and lysosome and keeps the hydrolytic enzymes contained from the outside components
• OM of the autolysosome --> degradation contents stay inside and selectively recognises damaged proteins via membrane proteins
• As the autolysosome forms remember that the proteins expressed on the lysosome changes however, the amount of LC3-ii is a key marker as its present in almost all stages exception of the phagophore.