Ion Homeostasis of Endolysosomes in Neurological Diseases

Dear Colleagues,

Consisting of a heterogeneous group of acidic organelles, the endolysosomal system is a dynamic interconnected network that exhibits complex interactions with other organelles. The endolysosomal system is critical for cellular homeostasis and supports diverse cellular functions, including macromolecule degradation via endocytosis or autophagy, nutrient recycling and sensing, plasma membrane repair and remodeling of the extracellular matrix, and signaling. Equivalent to extracellular space, endolysosomal lumen contain various ions including H⁺, Na⁺, K⁺, Ca²⁺, Cl⁻, and metal ions (Fe²⁺, Zn²⁺, Cu²⁺). Proper luminal ionic homeostais is critical for endolysosome function, and ionic movements through various channels and transporters located on the endolysosomal membrane function as signals that help orchestrate diverse cellular functions supported by endolysosomes. As such, disturbed luminal ionic homeostasis and dysregulation of ion movement across endolysosomal membrane impairs many aspects of endolysosomal function, including its degradation capability, mobility, position, fusion and fission, nutrient sensing, biogenesis, and inter-organellular cross talk.

Endolysosomes are especially important for neurons because they are long-lived post-mitotic cells with that require constant vesicular membrane trafficking. Endolysosomal dysfunction, including disturbed endolysosomal ionic homoestais, has been observed in various neurological disorders. Understanding how altered endolysosomal ionic homoestais leads to neurolgical dsyfunction will provide mechansitic insights into the pathogenesis of neurological disorders. On the other hand, re-establishing proper endolysosomal ion homeostasis and fine-tuning ionic movement across endolysosomal membrane represents a promising therapeutic strategy against neurological disorders.

The aim of this Special Issue of Cells is to collect current knowlege and recent advances in the field of endolysosomal ion homeostasis in neurological disorders. Therefore, we invite you to contribute papers in the form of original research articles, reviews, or shorter perspective articles on all aspects related to the role of endolysosomal ion in neuronal physiology and pathophysiology. Expert articles describing future therapeutics are especially welcome.

Dr. Xuesong Chen
Guest Editor

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• Endolysosome
• Ion homeostasis
• Metal ion
• Neuron
• Neurological disorders