AUTOPHAGY PATHWAY, A RECYCLING SYSTEM IN CELLS

Autophagy pathway is an adaptive process in response to cellular stress as nutrient starvation, oxidative stress, hypoxia, protein aggregation... It prevents cell damage and promote cell survival. It is a crucial molecular pathway for the preservation of cellular and organismal homeostasis ^(1,2).

During this process, key autophagic factors (ATG) orchestrate the formation of a double-membrane vesicle, known as the autophagosome. This encapsulates cellular components and fuses with lysosomes, resulting in the degradation of its contents through the activities of lysosomal hydrolases. The control of these factors is very important to ensure cellular homeostasis ⁽³⁾.

• In macro-autophagy, a membrane structure resembling a cup, appears close to the endoplasmic reticulum (ER). It referred to as the phagophore or isolation membrane. It undergoes elongation, bending, and eventually closes through membrane fission.

  This leads to the formation of a double-membraned structure known as the autophagosome. This autophagosome encapsulates a portion of the cytoplasm. Subsequently, the autophagosome merges with lysosomes (or vacuoles in yeasts and plants), which break down the contents.

  The ULK complex is the central regulator in the beginning of macro-autophagy. It contains the scaffold protein FIP200 (also known as RB1CC1), ATG13, ATG101 and the serine/threonine kinases ULK1 or ULK2. Mainly, mechanistic target of rapamycin complex 1 (mTORC1) inhibits its activity.

• In micro-autophagy, the endosomal or lysosomal membrane invaginates inward to directly capture part of the cytoplasm.

  Endosomal micro-autophagy, a form of micro-autophagy in mammalian cells, involves the formation of multivesicular bodies within endosomes.

  The endosomal micro-autophagy occurs naturally. It also triggers during early periods of amino acid starvation. This process helps break down certain proteins found in the cytoplasm. Specifically, adaptors involved in macro-autophagy, like SQSTM1, NDP52, NBR1, TAX1BP1, and NCOA4, which is responsible for ferritin ⁽⁹⁾.