Autophagy

Autophagy is an adaptive process in response to cellular stress (nutrient starvation, oxidative stress, hypoxia, protein aggregation,...) to prevent cell damage and promote cell survival ^(1,2).

Key autophagic factors induce these autophagic mechanisms resulting in the processing and degradation of damaged material by autolysosomes ⁽³⁾. These factors need to be tightly controlled to ensure cellular homeostasis.

The dysregulation of autophagic process is now known to be involved in many pathologies ⁽⁴⁾ including :

• infectious diseases ⁽⁵⁾
• cancer ⁽⁶⁾ with pro- and anti-tumoral complex roles, notably in inflammation, cell migration...
• neurodegenerative diseases ^(7-8) with defects to eliminate misfolded toxic protein aggregates and damaged mitochondrion (Parkinson, SLA...) ⁽²⁾.
  

A recent study on replicative crisis suggests that autophagy is an integral component of the tumor suppressive crisis mechanism and that loss of autophagy function is required for the initiation of cancer.
Crisis was associated with an increase in the autophagy-related proteins lysosomal-associated membrane protein 1 (LAMP1), ATG5–ATG12 conjugate (for phagophore biogenesis) and the lipidated form of microtubule-associated protein 1A/1B-light chain 3 (LC3), LC3-II (for phagophore expansion), whereas the autophagy target polyubiquitin-binding protein P62 (also known as SQSTM1) was reduced ⁽⁹⁾.