Figure 11.

Schematic diagram outlining HIV-1 TAT-mediated defective mitophagy and microglial activation. Exposure of microglial to HIV-1 TAT decreases mitochondrial membrane potential, leading in turn, to mitochondrial dysfunction, that was followed by initiation of mitophagy and mitophagosomes formation. Exposure to HIV-1 TAT, however, blocked mitophagosome maturation, thereby leading to impaired clearance of damaged mitochondria. Accumulation of mitophagosome due to defective mitophagy resulted in microglial activation and increased the release of proinflammatory cytokines, leading to neuroinflammation.