Autophagy

what is autophagy?

the process by which entire worn-out organelles, proteins, or enzymes are digested

- highly regulated lysosomal pathway

- helps maintain cell homeostasis and metabolism

- evolutionarily conserved

autophagy is a response to ____________ stress

nutrient stress

- allows the cell to survive and maintain adequate internal levels of nutrients via self-cannibalization

- in nutrient-rich conditions, autophagy promotes cell death in response to other stressors

what role does autophagy play in cell death?

role is best revealed when apoptosis is disabled!

- possesses important cross-talk and interrelationships with apoptosis and senescence

what are some things that can trigger autophagy?

- starvation

- ER stress

- natural processes

- mechanical stress

- organelle damage

- cytotoxicity

- hypoxia

- infection

what are some effects that autophagy has on the cell/body?

plays a role in...

- immunity

- development/differentiation

- longevity

- energy homeostasis

- protein turnover/quality control

- pathogen and organelle removal/defense

- nutrient recycling

- stress adaptation

- inflammation

- cell death

what is the functional unit of autophagy?

autophagosome

- double-walled vesicle that is created in the cytoplasm

- encapsulates cytoplasmic cargoes (organelles, inclusions, etc.) and delivers them to the lysosome for degradation

during autophagy, the cytosolic form of __________ undergoes proteolysis and lipidation

LC3

- LC3-I undergoes C-terminal proteolysis and lipidation (LC3-II) and translocates to the autophagosomal membrane

- LC3 is used as a specific marker of autophagy

what occurs within an autophagosome once it is fully formed?

the inner membrane of the autophagosome and the cellular materials within the autophagosome are degraded by the lysosomal/vacuolar hydrolases within

what is the relationship between autophagy and apoptosis? provide examples

they inhibit each other! (but share common inducers and regulators)

- autophagy of mitochondria (mitophagy) inhibits mitochondrial-induced apoptosis (intrinsic pathway)

- autophagy of zymogen granules (zymophagy) inhibits acinar cell damage and necrosis in pancreatic tissues

- senescence-induced autophagy inhibits oncogene-mediated transformation

genetic analysis of yeast lead to the discovery of ___________

autophagy-related genes (ATGs)

what protein triggers autophagy?

vacuole membrane protein 1 (VMP1)

- autophagy is blocked in its absence

- required for the biogenesis of autophagosome in mammalian cells

T/F: autophagy may play a role in development of disease

TRUE

- may influence the pathogenesis of human diseases like cancer and neurodegenerative/inflammatory/metabolic diseases

what was Yoshinori Ohsumi's research that earned him a Nobel Prize?

Japanese cell biologist

- researched how cells recycle and renew their content (autophagy)

- found that fasting activates autophagy, which helps slow down the aging process and has a positive impact on cell renewal

- discovered that autophagy genes are used by higher organisms including humans, and that mutations in these genes can cause disease