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Printable Handouts
Navigable Slide Index
- Introduction
- Autophagy is a cytosolic degradative pathway
- Autophagy inputs and outputs
- Two roles of autophagy in homeostasis
- Selective autophagy is important for health
- The mammalian autophagy pathway
- A ubiquitin-like conjugation reaction
- Cargo receptors
- Cargo receptors may have multiple functions
- Examples of cargo receptor functions
- Example 1: p62 in aggrephagy
- p62 binds poly-ubiquitinated proteins
- p62 LIR motifs
- Avidity effects and autophagosome formation
- Cargo receptor disruption and disease
- Example 2: xenophagy of Salmonella
- TAX1BP1, NDP52 and Optineurin binding
- Non-canonical LIR motif
- Stimulatory signals for selective autophagy
- Example 3: Mitophagy
- PINK/Parkin-dependent mitophagy (1)
- PINK/Parkin-dependent mitophagy (2)
- Parkin-independent mitophagy
- Non-proteinaceous cargo receptors
- Effector roles of receptors in selective mitophagy
- Example 4: ER-phagy
- Further nuances of receptor function
- Receptors as sensors of stress
- ATG proteins and selecetive autophagy
- Effector roles of receptors in ER-phagy
- ER-phagy and tissue-specificity of receptors
- Other forms of selective autophagy
- Conclusions
- Thank you
Topics Covered
- Selective autophagy mechanisms and importance for health
- Principles of action of cargo receptors
- p62 and aggrephagy
- LIR motifs
- Salmonella and xenophagy
- Mitophagy
- Erphagy
Talk Citation
Wilkinson, S. (2018, October 31). Cargo receptors for selective autophagy [Video file]. In The Biomedical & Life Sciences Collection, Henry Stewart Talks. Retrieved November 21, 2024, from https://doi.org/10.69645/MFSD1332.Export Citation (RIS)
Publication History
Financial Disclosures
- Dr. Simon Wilkinson has not informed HSTalks of any commercial/financial relationship that it is appropriate to disclose.
Other Talks in the Series: Autophagy and Lysosomal Storage Diseases
Transcript
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0:00
Hello.
I'm Simon Wilkinson from the University of Edinburgh and today,
I'm going to tell you all about structure, function and physiological role of
a classic molecule, known as cargo receptors, which
mediate a number of homeostatic processes,
collectively known as selective autophagy.
0:20
Macroautophagy or as I shall refer to it from here on in, autophagy,
is the major pathway for degradation of cytosolic multi-molecular complexes. Whereas
proteases such as site-specific proteases or
the proteasome tend to act upon single polypeptide molecules.
The autophagy pathway encapsulates organelles,
pathogens and large protein complexes in vesicles called
autophagosomes that are destined for degradation via fusion with lysosomes.
0:53
Autophagy thus serves several purposes.
The metabolites released from lysosomal degradation of the cargos of autophagy,
and we defined cargos here as the organelle,
pathogen or protein complexes encapsulated into the autophagosomes, and feed into
recycling into new structures via anabolic pathways or catabolism to produce energy.
However autophagy also, and this is the critical subject of today's lecture,
results in removal from the cytosolic milieu of the cell of these cargos.
1:30
In fact autophagy to feed metabolism tends to operate under
nutrient stress and in this instance cargos are sacrificed in a non-selective manner.
Effectively autophagy catabolises bulk cytosol in order to keep cells alive.
However we're interested today in selective autophagy.
This is where autophagic degradation specifically targets unwanted cargos in order to
remove them selectively from the cytosol
of cells and this is critical for cellular health.