Autophagy II Flashcards
What is Huntingtons caused by?
PolyQ expansion in huntington protein.
What are normal / not normal levels of polyQ?
Q<18 = normal
Q>35 = disease
What happens in Huntingtons?
Protein misfolds
Aggregation
(Small proteins get degraded by proteosome)
Ubiquitination, forms aggresome.
Gets degraded by macroautophagy.
How many people out of 100 get parkinsons in the UK?
1-2
What is Parkinsons caused by?
Aggregates of alpha synuclein.
Alpha synuclein is usually degraded by chaperon mediated autophagy, but mutated versions block MCA which causes toxicity.
What does damaged mitochondria cause?
Damaged mitochondria accumulates, which accumulates ROS which damages cellular components.
What is ROS?
Reactive oxygen species
What is mitophagy?
Autophagy of mitochondria
What proteins regulate mitophagy?
PINK1 and PARKIN
PINK1: mitochondrial kinase
PARKIN: cytosolic ubiquitin ligase
What happens when PINK1 and PARKIN are not functioning?
Damaged mitochondria are not degraded. Increases ROS, more damaged mitochondria.
What role does autophagy play in cancer?
Autophagy is tumour suppressive (and apoptosis suppressive)
What is Beclin1 required for?
Autophagosome formation
What conditions is autophagy unregulated in?
Hypoxic, low nutrient tumour conditions
What does Bcl2 do?
Binds to mitochondria and prevents the release of cytokines which cause apoptosis.
How does autophagy supress apoptosis?
Beclin1 is involved in autophagy. Bcl2 supresses apoptosis.
If Beclin1 and bCL2 bind, autophagy is supressed and apoptosis occurs.
