Figure 2.

Cellular events involved in NPC1 disease: (a) cholesterol accumulation in lysosomes due to the loss of function of the cholesterol (ch) transporter NPC1; (b) autophagy/mitophagy blockade and accumulation of indigested autophago-lysosomes due to lysosomal accumulation of ch, ch-induced hyperactivation of the anti-autophagy complex mTORC1; (c) accumulation of dysfunctional mitochondria due to accumulation of ch in mitochondria and mitophagy blockade; (d) ATP production decrease and ROS increase by dysfunctional mitochondria; (e) loss of lysosomal ionic homeostasis. Blue pentagons: cholesterol.