BCH3021 Lecture Notes - Lecture 23: Atg8, Mitophagy, Autophagy
Lecture 23 – Autophagy II – Selective Forms
Mitophagy
Xenophagy – autophagy combats intracellular pathogens (foreign): bacteria/viruses
• Bacteria uses it as niche to survive in cell
A model for Selectivity – Yeast (Biosynthetic pathway)
• ATG’s are required to deliver hydrolases to yeast vacuole (CT pathway:
cytosome to chromatin.
• Two hydrolases are delivered in autophagosomes in vacuole
• Delivery – cargo specific
• Cargo receptor (Atg19): protein that recognises cargo
Receptor Protein Complexes Control Selective Autophagy
• Cargo → ligand → receptor→ scaffold and ATG8
o Ligand-receptor interaction is important for selectivity
• Receptor motif interacts with ATG8
• Receptor interacts with ATG8/LC3 through LC3 Interacting Domain (LIR)
Range of Different Autophagy Receptors Allow
• Individual targets to be selected to exclusion of others
• Individual targets to be selected at different times, in different tissues for
different reasons
• Mitochondria are subject to autophagy because
o Excess to requirement
o Development
o Damage
Example: Mitophagy in Yeast
• Atg32 is anchored in outer membrane of mitochondria (c-terminal anchor)
o Motif allows it to interact with Atg8 through cytosolic LIR domain
o Signal induces phosphorylation of exposed Atg32 cytosolic promoting
interaction with Atg11
• Kinase X interacts with phosphate
• Cells lacking ATG32 expression – defective for selective autophagy
• Genes categorised into: Selective autophagy-specific, core machinery and
nonselective autophagy specific
Non-selective Autophagy
Selective Autophagy
• Nutrient deprivation conditions
• Provides energy and building blocks
• Nutrient rich conditions
o Excludes anything else from
phagosomes
o Liver cells rely on peroxisomes
– need to turn them over
• Cargo specific
• E.g. pexophagy removes peroxisomes
on change of carbon source – methanol
to glucose in yeasts → don’t need them
• Tissue specific examples where
organelles need to be removed
find more resources at oneclass.com
find more resources at oneclass.com
Document Summary
Lecture 23 autophagy ii selective forms. Xenophagy autophagy combats intracellular pathogens (foreign): bacteria/viruses. Bacteria uses it as niche to survive in cell. Selective autophagy: nutrient deprivation conditions, provides energy and building blocks, nutrient rich conditions, excludes anything else from phagosomes, liver cells rely on peroxisomes. Need to turn them over: cargo specific, e. g. pexophagy removes peroxisomes on change of carbon source methanol to glucose in yeasts don"t need them, tissue specific examples where organelles need to be removed. Receptor protein complexes control selective autophagy: cargo ligand receptor scaffold and atg8, ligand-receptor interaction is important for selectivity, receptor motif interacts with atg8, receptor interacts with atg8/lc3 through lc3 interacting domain (lir) Individual targets to be selected to exclusion of others. Individual targets to be selected at different times, in different tissues for different reasons: mitochondria are subject to autophagy because, excess to requirement, development, damage. Atg6/lc3 pathway: lc3 is only atg protein known to remain associated with completed autophagosomes.
