ArticleThe Journal of cell biology2023
Lysosomal chloride transporter CLH-6 protects lysosome membrane integrity via cathepsin activation.
Article in The Journal of cell biology, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.
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Who cites it
18 citing papers in PubMed, 25 citations in OpenAlex.
- CLN3 mediates chloride efflux from lysosomes.Neuron · 2026Article
- Enhancing biological imaging with high-performance probes based on thermally activated delayed fluorescence.iScience · 2025Review
- Lysosomal ion channels and pain.Pain reports · 2025Review
- Sorting nexin 10 regulates lysosomal ionic homeostasis via ClC-7 by controlling PI(3,5)P2.The Journal of cell biology · 2025Article
- The autophagy protein ATG-9 regulates lysosome function and integrity.The Journal of cell biology · 2025Article
- The autophagy protein ATG-9 regulates lysosome function and integrity.The Journal of cell biology · 2025Article
- FRET-based reporter assesses lysosomal DNA-degradation ability in live cells.Sensors and actuators reports · 2025Article
- The spectrum of lysosomal stress and damage responses: from mechanosensing to inflammation.EMBO reports · 2025Review
- Article
- Cysteine protease cathepsin B promotes lysosome integrity to extend the lifespan of alternative day fasting worms.Aging cell · 2024Article
- Disturbed intracellular folate homeostasis impairs autophagic flux and increases hepatocytic lipid accumulation.BMC biology · 2024Article
- The ion channels of endomembranes.Physiological reviews · 2024Review
- The ion channels of endomembranes.Physiological reviews · 2024Review
- The ion channels of endomembranes.Physiological reviews · 2024Review
- Chloride Homeostasis Regulates cGAS-STING Signaling.bioRxiv : the preprint server for biology · 2024Article
- Article
- Impaired Autophagic Clearance with a Gain-of-Function Variant of the Lysosomal ClBiomolecules · 2023Article
- Tubular lysosome induction couples animal starvation to healthy aging.Nature aging · 2023Article
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Authors and funding
5 authors at 2 institutions in 1 country.
Funding
Abstract
Lysosomal integrity is vital for cell homeostasis, but the underlying mechanisms are poorly understood. Here, we identify CLH-6, the C. elegans ortholog of the lysosomal Cl-/H+ antiporter ClC-7, as an important factor for protecting lysosomal integrity. Loss of CLH-6 affects lysosomal degradation, causing cargo accumulation and membrane rupture. Reducing cargo delivery or increasing CPL-1/cathepsin L or CPR-2/cathepsin B expression suppresses these lysosomal defects. Inactivation of CPL-1 or CPR-2, like CLH-6 inactivation, affects cargo digestion and causes lysosomal membrane rupture. Thus, loss of CLH-6 impairs cargo degradation, leading to membrane damage of lysosomes. In clh-6(lf) mutants, lysosomes are acidified as in wild type but contain lower chloride levels, and cathepsin B and L activities are significantly reduced. Cl- binds to CPL-1 and CPR-2 in vitro, and Cl- supplementation increases lysosomal cathepsin B and L activities. Altogether, these findings suggest that CLH-6 maintains the luminal chloride levels required for cathepsin activity, thus facilitating substrate digestion to protect lysosomal membrane integrity.
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