Roles of Proteasome and Autophagy in Cell Maintenance Flashcards
(18 cards)
What is proteostasis?
The process of maintaining healthy and functional proteins in the cell.
What systems maintain proteostasis?
The ubiquitin–proteasome system (UPS) and autophagy.
What type of proteins does the proteasome degrade?
Short-lived, misfolded, and regulatory proteins.
What is required to target proteins for degradation by the proteasome?
Polyubiquitination (a chain of ubiquitin proteins attached to the target).
What is the role of the 26S proteasome?
It recognises polyubiquitinated proteins, unfolds them, and degrades them into peptides using ATP.
What does autophagy degrade?
Long-lived proteins, organelles, and protein aggregates.
How does autophagy work?
Material is enclosed in an autophagosome, which fuses with a lysosome, where degradation occurs.
What regulates autophagy?
mTOR (inhibits), AMPK (activates), and nutrient status.
How do UPS and autophagy differ?
UPS: fast, selective, degrades small cytosolic proteins.
Autophagy: slower, degrades large structures, aggregates, organelles.
What happens when these systems fail?
Accumulation of damaged proteins and organelles → linked to diseases like Alzheimer’s, Parkinson’s, and cancer.
How might these systems be targeted in therapy?
Enhancing autophagy or proteasome function could help delay ageing, treat neurodegeneration, and control cancer.
What should go in the introduction of an essay on proteostasis?
Define proteostasis as protein quality control.
Introduce the two major degradation pathways: the proteasome and autophagy.
Explain their importance in cellular maintenance and stress response.
What are the key points to include about the proteasome?
Degrades misfolded, short-lived, regulatory proteins.
Requires polyubiquitination.
Uses the 26S proteasome to unfold and degrade proteins into peptides.
ATP-dependent process in the cytosol and nucleus.
What should be included about autophagy?
Handles long-lived proteins, aggregates, and organelles.
Cargo enclosed in autophagosome → fuses with lysosome.
Regulated by mTOR, AMPK, and nutrient status.
Slower and bulkier than proteasomal degradation.
How should you compare the proteasome and autophagy?
Proteasome: selective, fast, ATP-dependent, cytosolic proteins.
Autophagy: bulk degradation, slower, handles organelles and large complexes.
Both are crucial but serve different roles.
What are the links between ageing, disease, and these pathways?
Both decline with age.
UPS failure → protein aggregation (Alzheimer’s, Parkinson’s).
Autophagy failure → defective organelle clearance, tumour progression.
Impaired proteostasis = cellular dysfunction.
What therapeutic angles should be discussed?
Autophagy enhancers (e.g., rapamycin)
Modulating UPS in cancer or neurodegeneration
Potential for targeted therapies to restore balance.
What should go in the conclusion of an essay on proteostasis?
Proteasome and autophagy maintain cellular quality control.
Their failure leads to disease and ageing.
Therapeutic modulation of these pathways offers real promise.
