Autophagy and Its Lineage-Specific Roles in the Hematopoietic System

Figure 2

Macroautophagy and its role in hematopoiesis. During macroautophagy, AMPK activates the ULK1 complex and consequently induces the membrane isolation process where PI3Ks and ATG9 take part as positive regulators and enable autophagosome formation with the aid of ATG12-ATG5 and the LC3 conjugation systems. The ATG5–ATG12–ATG16L1 complex induces LC3 conjugation, whereas LC3 is cleaved by ATG4 protease to form LC3-I, and cytosolic LC3-1 is further conjugated with PE to form LC3-II. Afterward, autophagosomes come in contact with the lysosome which has the hydrolase enzymatic activity to fuse with autophagosome to form autolysosome for cytosolic cargo degradation. The normal state of autophagic activity is essential for the maintenance of blood cell homeostasis. Defective autophagy results in imbalanced hematopoiesis and impeded HSCs’ self-renewal, leading to the generation of malignant blood cell types.