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However, the exact way NNMT works still needs more exploration, and further studies are needed to fully understand and develop treatments focused on NNMT
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In many experimental models, this stage is disrupted: lysosomal enzymes are prematurely activated or mislocalized, lysosomal membrane integrity is compromised, and lysosomeautophagosome fusion is impaired, all of which lead to accumulation of large autophagic vacuoles and impaired PAC function ( Thus, functional crosstalk between mitochondria and lysosomes via autophagy and mitophagy represents a double-edged mechanism: it can protect PACs by removing damaged organelles but, when dysregulated, is associated with accumulation of dysfunctional mitochondria, amplification of ROS and DAMP signaling, and a shift from adaptive stress responses to irreversible cell death ( Mitochondrial quality control is determined not only by lysosomal competence but also by the cytoskeletal architecture that spatially organizes mitochondria, autophagosomes, and lysosomes within PACs
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