title: Regulation of lysosomal ion homeostasis by channels and transporters.
abstract: Lysosomes are the major organelles that carry out degradation functions. They integrate and digest materials compartmentalized by endocytosis, phagocytosis or autophagy. In addition to more than 60 hydrolases residing in the lysosomes, there are also ion channels and transporters that mediate the flux or transport of H(+), Ca(2+), Na(+), K(+), and Cl(-) across the lysosomal membranes. Defects in ionic exchange can lead to abnormal lysosome morphology, defective vesicle trafficking, impaired autophagy, and diseases such as neurodegeneration and lysosomal storage disorders. The latter are characterized by incomplete lysosomal digestion and accumulation of toxic materials inside enlarged intracellular vacuoles. In addition to degradation, recent studies have revealed the roles of lysosomes in metabolic pathways through kinases such as mechanistic target of rapamycin (mTOR) and transcriptional regulation through calcium signaling molecules such as transcription factor EB (TFEB) and calcineurin. Owing to the development of new approaches including genetically encoded fluorescence probes and whole endolysosomal patch clamp recording techniques, studies on lysosomal ion channels have made remarkable progress in recent years. In this review, we will focus on the current knowledge of lysosome-resident ion channels and transporters, discuss their roles in maintaining lysosomal function, and evaluate how their dysfunction can result in disease.
authors.affiliation: Department of Integrative Biology and Pharmacology, McGovern Medical School, Program of Cell and Regulatory Biology, Graduate School of Biomedical Sciences, The University of Texas Health Science Center at Houston, Houston, 77030, USA.
authors.forename: Jian
authors.initials: J
authors.lastname: Xiong
authors.affiliation: Department of Integrative Biology and Pharmacology, McGovern Medical School, Program of Cell and Regulatory Biology, Graduate School of Biomedical Sciences, The University of Texas Health Science Center at Houston, Houston, 77030, USA. Michael.x.zhu@uth.tmc.edu.
authors.forename: Michael X
authors.initials: MX
authors.lastname: Zhu
mesh_terms: D006706:Homeostasis; D006801:Humans; D006863:Hydrogen-Ion Concentration; D007425:Intracellular Membranes / Q000378:metabolism; D007473:Ion Channels / Q000378:metabolism*; D017136:Ion Transport; D007477:Ions / Q000378:metabolism*; D008247:Lysosomes / Q000737:chemistry / Q000378:metabolism*; D026901:Membrane Transport Proteins / Q000378:metabolism*; D008954:Models, Biological
chemical_list: D007473:Ion Channels; D007477:Ions; D026901:Membrane Transport Proteins
keywords: calcium; ion homeostasis; lysosomal storage disease (LSD); lysosome acidification