Xinghua Feng*, Zhuangzhuang Zhao, Qian Li and Zhiyong Tan Pages 261 - 266 ( 6 )
Background & Objective: The lysosome is a membrane-enclosed organelle widely found in every eukaryotic cell. It has been deemed as the stomach of the cells. Recent studies revealed that it also functions as an intracellular calcium store and is a platform for nutrient-dependent signal transduction. Similar with the plasma membrane, the lysosome membrane is furnished with various proteins, including pumps, ion channels and transporters. So far, two types of lysosomal potassium channels have been identified: large-conductance and Ca2+-activated potassium channel (BK) and TMEM175. TMEM175 has been linked to several neurodegeneration diseases, such as the Alzheimer and Parkinson disease. Recent studies showed that TMEM175 is a lysosomal potassium channel with novel architecture and plays important roles in setting the lysosomal membrane potential and maintaining pH stability. TMEM175 deficiency leads to compromised lysosomal function, which might be responsible for the pathogenesis of related diseases. BK is a well-known potassium channel for its function on the plasma membrane. Studies from two independent groups revealed that functional BK channels are also expressed on the lysosomal plasma membrane. Dysfunction of BK causes impaired lysosomal calcium signaling and abnormal lipid accumulation, a featured phenotype of most lysosomal storage diseases (LSDs). Boosting BK activity could rescue the lipid accumulation in several LSD cell models. Overall, the lysosomal potassium channels are essential for the lysosome physiological function, including lysosomal calcium signaling and autophagy. The dysfunction of lysosomal potassium channels is related to some neurodegeneration disorders.
Conclusion: Therefore, lysosomal potassium channels are suggested as potential targets for the intervention of lysosomal disorders.
BK Channels, lysosomal potassium channels, lysosomal storage diseases, neurodegeneration diseases, TMEM175, potential targets.
Collaborative Innovation Center of Yangtze River Delta Region Green Pharmaceuticals, College of Pharmaceutical Sciences, Zhejiang University of Technology, Hangzhou 310014, Collaborative Innovation Center of Yangtze River Delta Region Green Pharmaceuticals, College of Pharmaceutical Sciences, Zhejiang University of Technology, Hangzhou 310014, Collaborative Innovation Center of Yangtze River Delta Region Green Pharmaceuticals, College of Pharmaceutical Sciences, Zhejiang University of Technology, Hangzhou 310014, Department of Pharmacology and Toxicology and Stark Neurosciences Research Institute, Indiana University School of Medicine, Indianapolis, IN, 46202