Endocytosis, ESCRT, and Autophagy: Cell Degradation Pathways

What is endocytosis?

The process by which cells internalise extracellular molecules and plasma membrane components into vesicles.

What are the main types of endocytosis?

Clathrin-mediated, caveolin-mediated, phagocytosis, and pinocytosis.

What is the main destination of endocytic vesicles?

The lysosome, for degradation and recycling of cargo.

What are the intermediate compartments in the endocytic pathway?

Early endosomes, late endosomes, recycling endosomes, and multivesicular bodies (MVBs).

What is the role of the early endosome?

It acts as a sorting station for internalised cargo and determines whether cargo will be recycled or degraded.

What is the function of the recycling endosome?

It returns receptors and lipids back to the plasma membrane.

What is a multivesicular body (MVB)?

An endosomal compartment containing intraluminal vesicles formed by inward budding of the endosomal membrane.

Why are MVBs important?

They sequester membrane proteins into internal vesicles, stopping receptor signalling and preparing cargo for degradation.

What happens to receptor-ligand complexes after internalisation?

They can either be recycled or sent to lysosomes for degradation.

How are activated receptors targeted for degradation?

By ubiquitylation, which serves as a signal for recognition by the ESCRT machinery.

What does ESCRT stand for?

Endosomal Sorting Complex Required for Transport.

What is the main function of the ESCRT complexes?

To form intraluminal vesicles within multivesicular bodies.

Which ESCRT complex binds ubiquitylated cargo?

ESCRT-0.

What phospholipid helps ESCRT-0 bind to the endosomal membrane?

Phosphatidylinositol 3-phosphate (PI3P).

What do ESCRT-I and ESCRT-II complexes do?

They help deform the membrane and recruit ESCRT-III.

What is the function of the ESCRT-III complex?

It drives membrane invagination and scission to form intraluminal vesicles.

What is the role of VPS4?

An ATPase that disassembles the ESCRT-III complex to recycle components after vesicle formation.

How does the ESCRT pathway terminate receptor signalling?

By internalising the receptor within an intraluminal vesicle, isolating it from the cytoplasm.

What is the connection between ESCRT machinery and viruses?

Some viruses (e.g. HIV) hijack ESCRT machinery for budding from the plasma membrane.

What phosphoinositide species is enriched in early endosomes?

PI(3)P (phosphatidylinositol 3-phosphate).

What is autophagy?

A lysosome-dependent degradation pathway for cytosolic components, damaged organelles, or pathogens.

What organelle is key to autophagy?

The autophagosome, a double-membraned vesicle that engulfs cytosolic material.

Where do autophagosome membranes originate from?

ER, Golgi, plasma membrane, or other intracellular membranes.

What happens to the autophagosome after formation?

It fuses with the lysosome for degradation of its contents.

What proteins are essential for autophagosome formation?

Atg8 (LC3) and the Atg5-Atg12-Atg16 complex.

What is the function of Atg8/LC3?

It decorates the autophagosomal membrane and helps recruit cargo.

What happens to Atg8/LC3 during autophagy?

It becomes lipidated and inserted into the autophagosomal membrane.

What is an amphisome?

A hybrid organelle formed by fusion of an autophagosome with an endosome or MVB before lysosomal fusion.

What are the two types of autophagy?

Non-selective (bulk cytosol degradation) and selective (targeted degradation).

When is non-selective autophagy activated?

During nutrient starvation to generate amino acids and energy.

How does selective autophagy recognise cargo?

Through autophagy receptors that bind both ubiquitin on cargo and LC3 on the autophagosome.

What is the function of autophagy receptors?

They link ubiquitinated cargo to the autophagosome membrane for degradation.

What is the end result of autophagy?

Degradation of cargo into amino acids and lipids, maintaining cellular homeostasis.