Chloroquine inhibits autophagic flux by decreasing autophagosome-lysosome fusion

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  1. futbablictalk Moderator

    Chloroquine inhibits autophagic flux by decreasing autophagosome-lysosome fusion


    Pharmacological modulators of this pathway have been extensively utilized in a wide range of basic research and pre-clinical studies. Bafilomycin A1 and chloroquine are commonly used compounds that inhibit autophagy by targeting the lysosomes but through distinct mechanisms.

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    We show that CQ mainly inhibits autophagy by impairing autophagosome fusion with lysosomes rather than by affecting the acidity and/or degradative activity of this organelle. Furthermore, CQ induces an autophagy-independent severe disorganization of the Golgi and endo-lysosomal systems, which might contribute to the fusion impairment. Autophagosome-lysosome fusion and autolysosome acidification constitute late steps in the autophagic process necessary to maintain functional autophagic flux and cellular homeostasis. Both of these steps are disrupted by the V-ATPase inhibitor bafilomycin A1, but the mechanisms potentially linking them are unclear. Inhibition of autophagosome-lysosome fusion by ginsenoside Ro via the ESR2-NCF1-ROS pathway sensitizes esophageal cancer cells to 5-fluorouracil-induced cell death via the CHEK1-mediated DNA damage checkpoint. Chloroquine inhibits autophagic flux by decreasing autophagosome-lysosome fusion. Mario Mauthe et al. Autophagy. Volume 14, 2018.

    To address this, we cultured primary rat cortical neurons from E18 embryos and used the Seahorse XF96 analyzer and a targeted metabolomics approach to measure the effects of bafilomycin A1 and chloroquine on bioenergetics and metabolism. Since it is now clear that mitochondrial quality control, particularly in neurons, is dependent on autophagy, it is important to determine whether these compounds modify cellular bioenergetics.

    Chloroquine inhibits autophagic flux by decreasing autophagosome-lysosome fusion

    IJMS Free Full-Text Autophagy in the Central Nervous., Bafilomycin A1 disrupts autophagic flux by inhibiting both.

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  6. SBI inhibits autophagy and. inhibits autophagic flux by decreasing autophagosome-lysosome fusion. Y. Accumulation of tau in autophagic vacuoles in chloroquine myopathy.

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    • Autophagosome-Lysosome Fusion - ScienceDirect.

    Chloroquine CQ, a 4-aminoquinoline compound, has long been prescribed for the treatment of malaria- 1, autoim mune disorders2 and viral infections 3. It functions primarily by inhibiting lysosomal proteases and blocking autophagosome-lysosome fusion 4. In the range of neutral pH, CQ can freely diffuse across the plasma membrane but Autophagic flux defects in cancer. The relationship between autophagy and tumorigenesis has been intensively explored, but whether autophagy plays a role of pro- or anti-tumorigenesis in tumor development and cancer therapy is still controversial 24. Several genetic links have been demonstrated between autophagic defects and cancer, implying that autophagy is a part of tumor suppressor pathways 25. Hence, development of specific autophagy modulators that do not perturb general endo-lysosomal traffic possesses unique challenges. In this article, we report a novel small molecule EACC that inhibits autophagic flux by blocking autophagosome–lysosome fusion.

     
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  8. relictum Well-Known Member

    Chloroquine - FDA prescribing information, side effects. Chloroquine does not treat the hypnozoite liver stage forms of Plasmodium and will therefore not prevent relapses of malaria due to P. vivax or P. ovale. Additional treatment with an anti-malarial agent active against these forms, such as an 8-aminoquinoline, is required for the treatment of infections with P. vivax and P. ovale.

    Chloroquine Oral Uses, Side Effects, Interactions, Pictures.