Autophagy Flashcards
What are the 2 main mechanisms of degradation?
The Ubiquitin/ Proteosome system (UPS), or Autophagy
How does the Ubiquitin System degrade material?
Ubiquitin targets specific proteins and this is recognised and degraded by a proteosome.
What is The Ubiquitin System often used for and why?
Signalling, as a specific protein can be degraded quickly (major turnover route for short-lived proteins).
What are the 3 types of Autophagy, and which is the main one?
- Macroautophagy (most common, the word autophagy almost always just refers to this)
- Chaperone-mediated autophagy
- Microautophagy
What are the mechanisms of Macroautophagy in 4 steps?
- Phagophore forms by expansion.
- Autophagosome forms by closure of phagophore.
- Autolysosome forms by fusion of lysosome and autophagosome (the cytosol acidifies here)
- Degradation of the materials inside the autolysosome by hydrolases and proteases.
What are 5 reasons cells need degradation?
- Homeostasis
- Signalling (used to down or up regulate)
- Reprogramming cells (allows different cells to have different cytosolic components/ differentiate)
- Removing damaged components
- Recycling nutrients (e.g. starvation)
How does Chaperone-mediated autophagy occur?
LAMP-2A receptor on lysosome recognises proteins and can enter it directly to be destroyed.
How does Microautophagy occur?
Cargo can be engulfed directly by lysosome membrane.
Which type of cell degradation doesn’t require lysosomes present?
The Ubiquitin/ proteasome system (UPS) uses proteosomes.
Why would The Ubiquitin/ proteasome system (UPS) be inefficient at degrading a lot of material at once?
As one proteosome degrades one protein at a time, many proteosomes would be needed.
What degradation pathway is most suitable for bulk digestion and removal of whole organelles?
Macroautophagy can degrade many proteins at once as well as whole organelles such as mitochondria.
What degradation pathway is most suitable for quick turnover of short lived proteins?
The Ubiquitin/ proteasome system (UPS), e.g. for signalling.
What degradation pathways are most suitable for long-lived proteins?
Chaperone-mediated autophagy and Microautophagy
Does the Chaperone-mediated autophagy and Microautophagy degrade individual proteins or bulk?
Individual proteins
What are the 4 key functions of Autophagy?
- Nutrient recycling
- Cellular remodelling
- Removal of damaged components
- Killing intracellular pathogens (mainly TB and salmonella in phagosome)
What is the effect of starvation of autophagy?
Autophagy is rapidly upregulated, as the digested material can be recycled.
What is an advantage to degradation with lysosomes?
The molecules released can support metabolism.
Why do cancer cells need autophagy to survive?
As cancer cells often undergo starvation due to having a lack of solid blood supply.
Why is (Macro) Autophagy used for cellular remodelling?
As this is the only mechanism to degrade whole organelles.
What are 2 examples of cellular remodelling by (Macro) Autophagy?
- Erythropoiesis (red blood cell differentiation)
>Red blood cells have no organelles, the nucleus is ejected by the mitochondria are cleared by autophagy. - Removal of sperm-derived mitochondria
>In fertilised egg mitochondria is removed from sperm via autophagy.
What are two ways mitochondria can be damaged and what happens to them once damaged?
> During exercise can sustain mechanical damage, or due to ROS can be chemically damaged.
> Autophagosomes degrade them.
What happens in terms of autophagy while we age?
Autophagy capacity decreases (as lysosomal capacity decreases), so cell damage accumulates quicker than at it can be removed.
Why are muscle and neuronal cells more susceptible to build up of damaged cells when aging?
As they are longer lived cells and highly active, so have more mechanical damage and more chance of mutation. So when autophagy capacity decreases, damaged cells will build up.