Mapping Cell-Type-Specific Lysosomal Content (renewed)

Mapping Cell-Type-Specific Lysosomal Content

In our recent manuscript (Ghoochani et al, Biorxiv, 2024), we developed a high-resolution lysosomal protein atlas from neurons, astrocytes, microglia, and oligodendrocytes. This comprehensive resource revealed the diverse and cell-type-specific lysosomal composition across brain regions. Notably, we identified dozens of previously uncharacterized lysosomal proteins, broadening our understanding of lysosomal compositions and functions. A key finding was the identification of SLC45A1 as a neuron-specific lysosomal protein whose mutations causes a neurological disease that we redefined as lysosomal storage disorder (LSD) through our work. Mechanistic studies demonstrated its dual role in V-ATPase stabilization and sugar transport, critical for lysosomal pH regulation and neuronal health. This discovery advances the understanding of lysosomal contributions to brain resilience and protection against neurodegeneration. As part of the second phase of this grant, we are performing similar studies on lysosomes from aged animals. Together with the Knight Initiative, we are developing public-facing internet resources to access all our experimental data to broaden the impact of our work.