Cell：大脑细胞类型特异性溶酶体蛋白图谱，揭示SLC45A1相关疾病属于溶酶体贮积症

Core Findings - The study provides a detailed protein atlas of lysosomes in various brain cell types, identifying previously unannotated lysosomal proteins and revealing the diversity of lysosomal composition across different brain cell types [4][10][11] - SLC45A1, a neuron-specific lysosomal protein, is redefined as a lysosomal storage disorder (LSD) due to its mutation leading to significant lysosomal dysfunction [4][8][16] Lysosomal Function and Importance - Lysosomes are membrane-bound organelles responsible for degrading macromolecules and clearing damaged organelles, crucial for maintaining cellular homeostasis [6] - They play a key role in nutrient and energy sensing pathways, impacting cellular metabolism and are involved in various cellular functions such as membrane repair and programmed cell death [6] Research Methodology - The research utilized a LysoTag mouse model combined with cell-type specific Cre recombinase expression to generate a comprehensive lysosomal protein map covering major brain cell types, including neurons, astrocytes, oligodendrocytes, and microglia [8][11] - The study highlights the impact of SLC45A1 on the stability of the V-ATPase complex on lysosomal membranes, linking its deficiency to impaired lysosomal acidification and mitochondrial dysfunction [4][8][16] Implications for Future Research - This research lays the groundwork for future studies on lysosomal biology and its role in neurodegenerative diseases, emphasizing the need to explore the specific functions of different lysosomal proteins in various brain cell types [11]