Figure 1.

Summary of mitochondrial events and general autophagic events under ApoE4 intervention. (A) After excessive cellular stress, mitochondria begin to swell and fragment into healthy mitochondria for fusion, and pre-degraded mitochondria for mitophagy. damaged mitochondria induce PINK1/Parkin pathways and then participate in general autophagic flux. ApoE4 is directly or indirectly involved in mitochondrial events, including DRP1 pathways during fission; the MFNs pathways during fusion; and the PINK1/Parkin pathways during mitophagic induction. (B) After excessive cellular stress, the omegasome is initiated to form an elongated into a phagophore, which encloses the damaged mitochondria and becomes a mature autophagosome. Lysosomes recruit to autophagosome and fuse with it to form autolysosome, the ultimate area of mitochondrial degradation. ApoE4 intervenes autophagic initiation by the mTOR, TFEB, and SIRT1 pathways; compromises elongation by LC3, p62, and Rab5 pathways; blocks autophagosome-lysosome fusion by the Rab7, LAMP2, and LAMP1 pathways; damages lysosomal degradation by CTSD and V-ATPase pathway.