Figure 5. . A working model to explain the ACAT1 blockage-dependent increase in autophagy and in lysosome biogenesis in microglia and in neurons.

ACAT1 blockage alters the local cholesterol content in MAM, which signals an increase in autophagosome formation. The increase in autophagosome formation leads to TFEB-mediated increase in lysosome biogenesis. ACAT1 blockage may also increase autophagosome-lysosome membrane fusion.

MAM: Mitochondria-associated ER membrane.