Autophagy
Exam: terminology + multiple-choice questions.
Definition
Autophagy = auto (oneself) + phagy (to eat) from “Greek”.
→ Referring to macro-autophagy.
= Evolutionarily conserved, highly regulated cellular process for bulky degradation of cytosolic
proteins and organelles.
→ Essential lysosomal degradation pathway for cell survival, differentiation, development, and
homeostasis.
= Cellular process for degrading and recycling intracellular components.
There are different forms of autophagy:
• Macro-autophagy
• Micro-autophagy
• Chaperone-mediated autophagy
Principe: recycling
Xenophagy = selective form of autophagy that targets and degrades invading pathogens like bacteria
and viruses.
Lipophagy = selective form of autophagy that breaks down lipid droplets.
Ribophagy = selective degradation of ribosomes.
Aggrephagy = targeted removal of protein aggregates via autophagy.
Mitophagy = selective autophagic degradation of damaged or excess mitochondria.
Pexophagy = selective form of autophagy by which peroxisomes are selectively degraded when they
are damaged or no longer needed.
Nucleophagy = selective form of autophagy that breaks down nuclear components, including
damaged DNA or parts of the nucleus.
Glycophagy = selective autophagic degradation of glycogen to release glucose.
Ferritinophagy = selective autophagic degradation of ferritin, the iron-storage protein, to release iron
and regulate cellular iron homeostasis.
,Macro-autophagy (or just autophagy): basics
Phases of the autophagic pathway:
• Initiation:
It starts with the formation of a preautophagosomal structure, which becomes an isolation
membrane or phagophore.
This membrane begins to surround the target material.
• Vesicle elongation:
The phagophore elongates and curves around the cargo, forming a double-membrane vesicle that
encloses the material = autophagosome.
• Maturation:
The autophagosome fully encloses the cargo.
• Docking and fusion:
The autophagosome then fuses with a lysosome, which contains lysosomal acid hydrolases enzymes
that will degrade the contents.
This fusion forms an autolysosome.
• Vesicle breakdown and degradation:
Inside the autolysosome, the contents are broken down by the enzymes.
The degraded materials are then released back into the cytoplasm for metabolic recycling, allowing
the cell to reuse the building blocks.
,Different types
There are 3 main types of autophagy:
• Chaperone-Mediated Autophagy (CMA):
Specific proteins containing a KFERQ-like motif are
recognized by the Hsc70 complex (= chaperone
protein).
These proteins are directly translocated across
the lysosomal membrane via LAMP-2A (= receptor
on the lysosome) for degradation.
No vesicle formation is involved. Only targeted,
selective import of unfolded proteins.
• Microautophagy:
The lysosomal membrane invaginates (folds inward) and engulfs small portions of the
cytoplasm directly.
The engulfed content is then degraded inside the lysosome.
This is a non-selective or mildly selective process that doesn’t require vesicle formation.
• Macroautophagy:
Double-membrane vesicles called autophagosomes form around cellular components.
These autophagosomes fuse with lysosomes, where their contents are degraded.
This method is capable of handling large cargo, including whole organelles.
The lysosome is the final destination in all 3 types.
It contains lysosomal hydrolases (enzymes) that break down the cargo into basic components
like amino acids (AA) and free fatty acids (FFA) for recycling.
Autophagy & pathogens
There are different ways to perform autophagy on pathogens (like bacteria):
• Xenophagy:
Autophagy targets and degrades intracellular pathogens by sequestering them in autophagosomes.
These fuse with lysosomes to form autolysosomes, where the pathogens are broken down.
, • Activation of innate immune system:
Viruses enter the cell and replicate, releasing viral nucleic
acids into the cytoplasm.
Autophagy sequesters this nucleic acid into vesicles that fuse
with endosomes, where TLR7 (= pathogen sensor) detects it.
This leads to the production of Type I interferons (IFN) =
antiviral signal.
• MHC Class II antigen presentation:
Autophagy captures cytosolic proteins, delivers them to
lysosomes, and breaks them into peptides.
These peptides are then loaded onto MHC class II
molecules for antigen presentation to immune cells.
→ Autophagy isn’t just for cleanup.
It helps degrade pathogens (xenophagy), boosts innate immune sensing of viral RNA, and aids
in adaptive immunity by generating peptides for MHC class II presentation.
Exam: terminology + multiple-choice questions.
Definition
Autophagy = auto (oneself) + phagy (to eat) from “Greek”.
→ Referring to macro-autophagy.
= Evolutionarily conserved, highly regulated cellular process for bulky degradation of cytosolic
proteins and organelles.
→ Essential lysosomal degradation pathway for cell survival, differentiation, development, and
homeostasis.
= Cellular process for degrading and recycling intracellular components.
There are different forms of autophagy:
• Macro-autophagy
• Micro-autophagy
• Chaperone-mediated autophagy
Principe: recycling
Xenophagy = selective form of autophagy that targets and degrades invading pathogens like bacteria
and viruses.
Lipophagy = selective form of autophagy that breaks down lipid droplets.
Ribophagy = selective degradation of ribosomes.
Aggrephagy = targeted removal of protein aggregates via autophagy.
Mitophagy = selective autophagic degradation of damaged or excess mitochondria.
Pexophagy = selective form of autophagy by which peroxisomes are selectively degraded when they
are damaged or no longer needed.
Nucleophagy = selective form of autophagy that breaks down nuclear components, including
damaged DNA or parts of the nucleus.
Glycophagy = selective autophagic degradation of glycogen to release glucose.
Ferritinophagy = selective autophagic degradation of ferritin, the iron-storage protein, to release iron
and regulate cellular iron homeostasis.
,Macro-autophagy (or just autophagy): basics
Phases of the autophagic pathway:
• Initiation:
It starts with the formation of a preautophagosomal structure, which becomes an isolation
membrane or phagophore.
This membrane begins to surround the target material.
• Vesicle elongation:
The phagophore elongates and curves around the cargo, forming a double-membrane vesicle that
encloses the material = autophagosome.
• Maturation:
The autophagosome fully encloses the cargo.
• Docking and fusion:
The autophagosome then fuses with a lysosome, which contains lysosomal acid hydrolases enzymes
that will degrade the contents.
This fusion forms an autolysosome.
• Vesicle breakdown and degradation:
Inside the autolysosome, the contents are broken down by the enzymes.
The degraded materials are then released back into the cytoplasm for metabolic recycling, allowing
the cell to reuse the building blocks.
,Different types
There are 3 main types of autophagy:
• Chaperone-Mediated Autophagy (CMA):
Specific proteins containing a KFERQ-like motif are
recognized by the Hsc70 complex (= chaperone
protein).
These proteins are directly translocated across
the lysosomal membrane via LAMP-2A (= receptor
on the lysosome) for degradation.
No vesicle formation is involved. Only targeted,
selective import of unfolded proteins.
• Microautophagy:
The lysosomal membrane invaginates (folds inward) and engulfs small portions of the
cytoplasm directly.
The engulfed content is then degraded inside the lysosome.
This is a non-selective or mildly selective process that doesn’t require vesicle formation.
• Macroautophagy:
Double-membrane vesicles called autophagosomes form around cellular components.
These autophagosomes fuse with lysosomes, where their contents are degraded.
This method is capable of handling large cargo, including whole organelles.
The lysosome is the final destination in all 3 types.
It contains lysosomal hydrolases (enzymes) that break down the cargo into basic components
like amino acids (AA) and free fatty acids (FFA) for recycling.
Autophagy & pathogens
There are different ways to perform autophagy on pathogens (like bacteria):
• Xenophagy:
Autophagy targets and degrades intracellular pathogens by sequestering them in autophagosomes.
These fuse with lysosomes to form autolysosomes, where the pathogens are broken down.
, • Activation of innate immune system:
Viruses enter the cell and replicate, releasing viral nucleic
acids into the cytoplasm.
Autophagy sequesters this nucleic acid into vesicles that fuse
with endosomes, where TLR7 (= pathogen sensor) detects it.
This leads to the production of Type I interferons (IFN) =
antiviral signal.
• MHC Class II antigen presentation:
Autophagy captures cytosolic proteins, delivers them to
lysosomes, and breaks them into peptides.
These peptides are then loaded onto MHC class II
molecules for antigen presentation to immune cells.
→ Autophagy isn’t just for cleanup.
It helps degrade pathogens (xenophagy), boosts innate immune sensing of viral RNA, and aids
in adaptive immunity by generating peptides for MHC class II presentation.
