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In microglia, HIV-1 Tat upregulates PTEN-induced kinase 1 (PINK1), Parkin RBR E3 ubiquitin protein ligase (PRKN), and dynamin-1-like protein (DNM1L), marking damaged mitochondria for turnover and promoting fission, yet sequestosome 1 (SQSTM1)-dependent flux is blocked, lowering the mitochondrial membrane potential and fostering microglial activation and neuroinflammation (Fig