Autophagy Flashcards
Unique role of autophagy
clears substrates that are too large to be degraded by the proteasome, including protein aggregates, organelles, amyloid fibril, bacteria and viruses
Proteostasis imbalance
leads to aggregates or even amyloid formation in cytoplasm
Autophagy definition
process by which the cell sequesters bulk damaged material in a double-membrane-bound organelle, called the autophagosome, and degrades it
Autophagy begins by…
initiation, and an isolation double-membrane, called the phagophore enriched in PI3P, beings to form, when vesicle is elongated it envelopes cytoplasmic contents and even whole organelles like mitochondria; proteins are recruited to vesicle as it matures to become autophagosome; lysosomes are recruited to the autophagosome and fuse with it
Lysosomes fuse with autophagosome
lysosomes contain a range of hydrolytic enzymes, like proteases and lipase, to destroy macromolecules inside
Three forms of autophagy
Macroautophagy, chaperone-mediated autophagy, microautophagy
Two main pathways converge on autophagosome formation
each recruit ubiquitin-like proteins to the membrane to drive autophagosome functions;
Autophagy receptors…
allow recruitment of diverse cargo into autophagosomes; molecules and proteins that are for specific autophagosomes so that cargo can be specific
BECN1 mutation
Involved in initiation of autophagy, deletion can significantly increase the risk of several types of cancer
Autophagy suppresses tumorigenesis after stress
normal tissue that experiences damage can be degraded by autophagy so it can be repaired
Impairment of autophagy during stress
impairment allows the damage to persist which can lead to tumorigenesis
Autophagy confers stress resistance on tumors
autophagy feeds tumors nutrients,
Bacteria can sabotage autophagy
can cleave LC3 from autophagosomes to inhibit degradation
