Science Note
[Jan. 3, 2024] Previous Science Note
Lysosomes in the Regulation of Metabolism and Organelle
Lysosomal dysfunction is increasingly recognized as a critical factor in the development and progression of several neurological diseases. In neurodegenerative diseases such as Parkinson's and Alzheimer's, impaired lysosomal function leads to the accumulation of misfolded proteins and neuronal toxicity, contributing to cell death and disease progression. Although rare, lysosomal storage diseases often have significant neurological manifestations due to the accumulation of undigested substances in neurons, impairing their function and survival. Therefore, understanding and targeting lysosomal pathways is emerging as a promising therapeutic approach to treat and potentially prevent a range of neurological disorders. |
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Lysosomes mediate the mitochondrial UPR via mTORC1-dependent ATF4 phosphorylation |
ARL8B mediates lipid droplet contact and delivery to lysosomes for lipid remobilization |
Nutrient-regulated control of lysosome function by signaling lipid conversion |
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Point of Interest - This phosphorylation of ATF4 triggers the mitochondrial unfolded protein response (UPRmt). - Interfering with the ability of mTORC1 to phosphorylate ATF4 inhibits the UPRmt. - The phosphorylation of ATF4 prevents ROS-induced cell death under mitochondrial stress. |
Point of Interest - ARL8B in its GDP-bound state associates with LDs, whereas ARL8B-GTP is predominantly associated with lysosomes. - ARL8B facilitates the contact between LDs and lysosomes, with both its GDP- and GTP-bound states forming a complex. - The ARL8B-mediated lysosomal lipolysis of LDs represents a pathway for the turnover of neutral lipids in macrophages. |
Point of Interest - Cells possess diverse lysosome populations, distinguished by the presence of either PI(3)P or PI(4)P. - A lipid switch, regulated by nutrient availability, facilitates the interconversion between these distinct lysosome populations. - mTORC1 signaling and the synthesis of lysosomal PI(4)P are mutually inhibitory, each suppressing the other's activity. |
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Related Techniques | ||||||||||||
Lysosomal function | Lysosomal Acidic pH Detection Kit-Green/Red and Green/Deep Red NEW | |||||||||||
Autophagy detection | DAPGreen / DAPRed (Autophagosome detection), DALGreen (Autolysosome detection) HOT | |||||||||||
Endocytosis detection | ECGreen-Endocytosis Detection | |||||||||||
Phagocytosis detection | AcidSensor Labeling Kit – Endocytic Internalization Assay and -Cellstain- Calcein-AM solution | |||||||||||
Mitophagy Detection | Mitophagy Detection Kit and Mtphagy Dye | |||||||||||
Mitochondrial superoxide detection | MitoBright ROS Deep Red - Mitochondrial Superoxide Detection | |||||||||||
Oxygen consumption rate assay | Extracellular OCR Plate Assay Kit | |||||||||||
Antibody/Protein labeling - fast and high recovery | Fluorescein, Biotin, and Peroxidase Labeling Kit - NH2 | |||||||||||
Related Applications | ||||||||||||
The simultaneous detection of lysosomal function with Mitochondrial ROS and intracellular Fe2+
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