Science Note
[Nov. 12, 2024] Previous Science Note
Lysosomal Dysfunction Drives Cell Senescence and Damage
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Recent research shows that lysosomal dysfunction in cells leads to toxic accumulation, causing stress responses, cell senescence and cell death. Here are some of the papers showing that lysosomal homeostasis is important for disease prevention. Lysosomal dysfunction disrupts essential cellular processes and leads to the promotion of several diseases, including neurodegenerative diseases and senescence. In neurodegenerative diseases such as Alzheimer's and Parkinson's, impaired lysosomal activity leads to the accumulation of toxic proteins that contribute to neuronal death and disease progression. Lysosomal dysfunction is also associated with cellular senescence, where it impairs the degradation of damaged cellular components, leading to the accumulation of senescent cells and promoting age-related diseases. Therapeutic strategies targeting lysosomal function are being explored to alleviate these conditions and improve overall cellular health. |
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PLD3 and PLD4 synthesize S,S-BMP, a key phospholipid enabling lipid degradation in lysosomes |
Modeling Parkinson’s disease pathology in human dopaminergic neurons by sequential exposure to α-synuclein fibrils and proinflammatory cytokines |
HKDC1, a target of TFEB, is essential to maintain both mitochondrial and lysosomal homeostasis, preventing cellular senescence |
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Point of Interest - PLD3 and PLD4 synthesize lysosomal S,S-bis(monoacylglycero)phosphate (BMP), which is critical for lipid degradation and brain health. - Lysosomal S,S-BMP is essential for lipid degradation; its synthesis by PLD3/4 prevents gangliosidosis and supports cellular health. - Mutations in PLD3 associated with neurodegenerative diseases reduce its activity, affecting S,S-BMP levels and contributing to lysosomal dysfunction. |
Point of Interest - Immune-induced lysosomal dysfunction promotes Lewy body (LB) formation in dopaminergic neurons, mimicking Parkinson's disease (PD) pathology. - α-Synuclein fibrils and immune challenges (e.g., interferon-γ treatment) induce LD-like inclusions in iPSC-derived dopaminergic neurons. - LB formation in PD may result from lysosomal-autophagic dysfunction, exacerbated by immune challenge and α-synuclein accumulation. |
Point of Interest - Mitochondrial and lysosomal functions are linked, with transcription factor EB (TFEB) and hexokinase domain containing 1 (HKDC1) playing critical roles in their regulation and maintenance. - HKDC1, regulated by TFEB, is essential for mitophagy and lysosomal repair, independent of its glycolysis function. - Loss of HKDC1 accelerates cellular senescence by causing mitochondrial hyperfusion and lysosomal damage. |
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| Related Techniques | ||||||||||
| Lysosomal function | Lysosomal Acidic pH Detection Kit -Green/Red and Green/Deep Red | |||||||||
| Mitophagy detection | Mitophagy Detection Kit | |||||||||
| First-time autophagy research | Autophagic Flux Assay Kit | |||||||||
| Autophagy detection | DAPGreen/ DAPRed (Autophagosome detection), DALGreen (Autolysosome detection) | |||||||||
| Cellular senescence detection | SPiDER-βGal for live-cell imaging or flow cytometry / microplate reader / tissue samples | |||||||||
| NEW SPiDER-βGal Blue for multiple staining with immunostaining and others | ||||||||||
| Lipid Droplet Staining | Lipi-Blue/ Green/ Red/ Deep Red | |||||||||
| Mitochondrial membrane potential detection | JC-1MitoMPDetection Kit,MT-1MitoMPDetection Kit | |||||||||
| Glycolysis/Oxidative phosphorylation Assay | Glycolysis/OXPHOS Assay Kit, Extracellular OCR Plate Assay Kit | |||||||||
| Total ROS detection | Highly sensitive DCFH-DA or Photo-oxidation Resistant DCFH-DA | |||||||||
| Mitochondrial superoxide detection | MitoBright ROS Deep Red - Mitochondrial Superoxide Detection | |||||||||
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| Related Applications | ||||||||||
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Lysosomal Function Analysis With existing reagents, it was difficult to determine whether lysosomal mass or their function (pH) fluctuated because the discussion was based on changes in the fluorescence brightness of a single dye. This kit contains pHLys Green, which is highly specific to lysosomes and shows pH-dependent changes in fluorescence, and pH-resistant LysoPrime Deep Red. Using these two dyes, lysosomal pH and volume of the same sample can be measured for a detailed analysis of lysosomal function. |
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Accurate Measurement for Lysosomal pH changes Existing lysosomal pH detection reagents have issues with dye localization, pH sensitivity, and retention. pHLys Green is a dye that solves these issues. The improved dye retention and localization enable detection of normal lysosomes, and the improved pH sensitivity enables detection of slight pH changes.
Product in Use: Related Product:
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