The hidden potential of lysosomal ion channels: A new era of oncogenes |
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| Institution: | 1. Departments of Physiology & Biophysics, Dalhousie University, Halifax, Nova Scotia, Canada;2. Departments of Biology, Dalhousie University, Halifax, Nova Scotia, Canada;1. Department of Integrative Biology and Pharmacology, University of Texas School of Medicine, Houston, TX 77030, United States;2. Graduate Program in Cell and Regulatory Biology, Graduate School of Biomedical Sciences, University of Texas School of Medicine, Houston, TX 77030, United States;3. Graduate Program in Neuroscience, Graduate School of Biomedical Sciences, University of Texas School of Medicine, Houston, TX 77030, United States;1. Center for Dementia Research, Nathan S. Kline Institute, Orangeburg, NY 10962, USA;2. Department of Psychiatry, New York University, New York, NY 10016, USA;3. Department of Pathology, New York University, New York, NY 10016, USA;4. Department of Cell Biology, New York University, New York, NY 10016, USA;5. Division of Pathophysiology and Repair, Cardiff University, Cardiff CF10 3XQ, UK;6. Department of Anatomy and Cell Biology, University of Pennsylvania, Philadelphia, PA 19104, USA;7. Department of Physiology, University of Pennsylvania, Philadelphia, PA 19104, USA;8. Pharmaceutical Science and Ophthalmology, University of Colorado, Aurora, CO 80045, USA;1. Munich Center for Integrated Protein Science CIPSM, Center for Drug Research, Ludwig-Maximilians-Universität, München, Germany;2. Department of Pharmacy, Center for Drug Research, Ludwig-Maximilians-Universität München, Germany |
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| Abstract: | Lysosomes serve as the control centre for cellular clearance. These membrane-bound organelles receive biomolecules destined for degradation from intracellular and extracellular pathways; thus, facilitating the production of energy and shaping the fate of the cell. At the base of their functionality are the lysosomal ion channels which mediate the function of the lysosome through the modulation of ion influx and efflux. Ion channels form pores in the membrane of lysosomes and allow the passage of ions, a seemingly simple task which harbours the potential of overthrowing the cell’s stability. Considered the master regulators of ion homeostasis, these integral membrane proteins enable the proper operation of the lysosome. Defects in the structure or function of these ion channels lead to the development of lysosomal storage diseases, neurodegenerative diseases and cancer. Although more than 50 years have passed since their discovery, lysosomes are not yet fully understood, with their ion channels being even less well characterized. However, significant improvements have been made in the development of drugs targeted against these ion channels as a means of combating diseases. In this review, we will examine how Ca2+, K+, Na+ and Cl− ion channels affect the function of the lysosome, their involvement in hereditary and spontaneous diseases, and current ion channel-based therapies. |
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| Keywords: | Ion channels Lysosomes Cancer Metastasis Chemotherapy Drug development Trpml TPCs BK channels ClC-7 TMEM175 |
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