Cancer Biology - Autophagy

what are 3 ways cancer cells achieve immortality?

telomeres, senescence, autophagy

what is autophagy?

process where cells eat themselves to recycle and regenerate themselves

what does autophagy promote?

homeostasis, differentiation, development and survival

what is compromised autophagy a hallmark of?

aging

where is autophagy conserved?

eukaryotic phylogenetic tree

what are the 6 steps of autophagy?

activation/initiation, nucleation, elongation, maturation, fusion, degradation

what occurs during the activation/initiation phase of autophagy?

stress activates AMPK and inhibits mTOR. AMPK phosphorylates ULK1.

what occurs during the nucleation phase of autophagy?

ULK1 activates Beclin-1 containing complex. Beclin-1 recruits WIPI. ATG5 containing vesicles are recruited by Beclin1/WIPI

what occurs during the elongation phase of autophagy?

membrane is extended by ATG-5 vesicles. LC3 selects targets for degradation. LC3 brings targets to “mouth”

what occurs during the maturation phase of autophagy?

“closing off” of “mouth” vesicle

what occurs during the fusion phase of autophagy?

SNARE proteins mediate fusion between lysosome and autophagy vesicle

what occurs during degradation phase of autophagy?

enzymes and acidic environment recycle materials

4 ways autophagy is involved in health and aging?

protein homeostasis, regulation of macromolecule availability, autophagy of damaged subcellular organelles, xenophagy

how is autophagy involved with protein homeostasis?

autophagy degrades misfolded proteins, removes large protein aggregates

how is autophagy involved with the regulation of marcromolecule availability?

glucose homeostasis, reduced fat accumulation

how is autophagy involved with the autophagy of damaged subcellular organelles?

disposes damaged organelles

what is mitophagy?

removal of damaged mitochondria

how is autophagy involved with xenophagy?

autophagy protects cell from infection

deficiencies in autophagy are ____ to cancer but autophagy ______ later cancer stages

linked to cancer, but autophagy helps fuel later stage cancers

how do deficiencies in autophagy prevent cancer?

prevent cancer by eating misfolded proteins before they progress too far

how do deficiencies in autophagy fuel LATER cancer stages?

recycling old mitochondria, allows cancer to stay alive under chemotherapy

what is the lysosome?

“garbage disposal” of the cell

what does the lysosome provide in the cell?

provides acidic environment inside the cell for degradative enzymes to function

what is the structure of lysosomes?

membranous sacs of hydrolytic enzymes

what does the lysosome control?

controls intracellular digestion of extracellular material and worn-out organelles

mnemonic to help remember the 6 steps of autophagy

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