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Lysosomes play a critical role in cellular metabolism and waste management. They are essential for maintaining cellular health and preventing the buildup of cellular waste, which can lead to disease and dysfunction. Understanding the functions of lysosomes is critical for developing treatments for a variety of diseases and disorders. Today, we introduce you to three highlighted articles focusing on lysosomal exocytosis, lysosomal AMPK pathway, and lysosomal pH optimization.
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Lysosomal exocytosis releases pathogenic α-synuclein species from neurons in synucleinopathy models
(Ying Xue Xie, et al., Nature Communications, 13, 4918, 2022)
- Pathogenic species of αSyn accumulate within neuronal lysosomes in mouse brains and primary neurons. - Neurons release these pathogenic αSyn species via SNARE-dependent lysosomal exocytosis - The released aggregates are non-membrane enveloped and seeding-competent - This release is dependent on neuronal activity and cytosolic Ca2+
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Low-dose metformin targets the lysosomal AMPK pathway through PEN2
(Teng Ma, et al., Nature, 603, 159-165, 2022)
- PEN2 is a binding partner of metformin with a dissociation constant at micromolar levels - Metformin-bound PEN2 forms a complex with ATP6AP1 which leads to the inhibition of v-ATPase and the activation of lysosomal AMPK - In vivo, liver-specific knockout of Pen2 abolishes metformin-mediated reduction of hepatic fat content, whereas intestine-specific knockout of Pen2 impairs its glucose-lowering effects. - Knockdown of pen-2 in Caenorhabditis elegans abrogates metformin-induced extension of lifespan
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Parkinson’s disease-risk protein TMEM175 is a proton-activated proton channel in lysosomes
(Meiqin Hu, et al., Cell, 185, 2292-2308, 2022)
- TMEM175 is the proton “leak” channel of lysosomes and endosomes - TMEM175 is a highly proton-selective channel that is gated by luminal protons - An endogenous lipid can also activate TMEM175 to trigger lysosomal proton release - TMEM175 sets the lysosomal pH optimum via a classic negative feedback mechanism
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Related Techniques
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- Lysosomal function assay
- Lysosomal pH and mass detection Kit HOT
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- Lysosome staining
- pH-dependent (Red) and pH-independent (Green / Deep Red) probes HOT
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- Autophagy detection
- DAPGreen / DAPRed (Autophagosome detection), DALGreen (Autolysosome detection)
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- Endocytosis detection
- ECGreen
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- Endocytosis detection
- ECGreen
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- Endocytic internalization assay
- AcidSensor Labeling Kit HOT
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- Extracellular vesicles labeling
- ExoSparkler Exosome Membrane Labeling Kit-Green, Red, Deep Red
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- Extracellular vesicles Isolation
- ExoIsolator Exosome Isolation Kit HOT
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- Total ROS detection
- Highly sensitive DCFH-DA or Photo-oxidation Resistant DCFH-DA
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