Figure 7.

Consequence of elevated cholesterol in ATAD3 disease. (1) Healthy control cell with normal cholesterol and lysosome levels (blue panel). In contrast, ATAD3 mutant cells (red panels) require more cholesterol than normal and the free cholesterol pool can be increased by reducing the number of cholesterol transporters (2), or remodelling cholesterol biosynthesis.⁶ The abundant free cholesterol leads to cholesterol aggregation in membranes and activation of the endolysosomal pathway to remove the aberrant membranes (3); however, cholesterol-engorged membranes are difficult to digest leading to many lysosomes with membrane whorls that are characteristic of lysosomal storage diseases (4).