title: Loss of membrane cholesterol influences lysosomal permeability to potassium ions and protons.
abstract: Cholesterol is an essential component of lysosomal membranes. In this study, we investigated the effects of membrane cholesterol on the permeability of rat liver lysosomes to K+ and H+, and the organelle stability. Through the measurements of lysosomal beta-hexosaminidase free activity, membrane potential, membrane fluidity, intra-lysosomal pH, and lysosomal proton leakage, we established that methyl-beta-cyclodextrin (MbetaCD)-produced loss of membrane cholesterol could increase the lysosomal permeability to both potassium ions and protons, and fluidize the lysosomal membranes. As a result, potassium ions entered the lysosomes through K+/H+ exchange, which produced osmotic imbalance across the membranes and osmotically destabilized the lysosomes. In addition, treatment of the lysosomes with MbetaCD caused leakage of the lysosomal protons and raised the intra-lysosomal pH. The results indicate that membrane cholesterol plays important roles in the maintenance of the lysosomal limited permeability to K+ and H+. Loss of this membrane sterol is critical for the organelle acidification and stability.
authors.affiliation: School of Life Sciences, Northeast Normal University, Changchun 130024, PR China.
authors.forename: Dong
authors.initials: D
authors.lastname: Deng
authors.forename: Nan
authors.initials: N
authors.lastname: Jiang
authors.forename: Shu-Jing
authors.initials: SJ
authors.lastname: Hao
authors.forename: Hui
authors.initials: H
authors.lastname: Sun
authors.forename: Guo-jiang
authors.initials: GJ
authors.lastname: Zhang
mesh_terms: D000818:Animals; D002784:Cholesterol / Q000737:chemistry* / Q000378:metabolism*; D006863:Hydrogen-Ion Concentration; D007425:Intracellular Membranes / Q000187:drug effects / Q000378:metabolism*; D007477:Ions; D008247:Lysosomes / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D010539:Permeability; D011188:Potassium / Q000737:chemistry / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar; D047392:beta-Cyclodextrins / Q000494:pharmacology
chemical_list: D007477:Ions; D047392:beta-Cyclodextrins; C108732:methyl-beta-cyclodextrin; D002784:Cholesterol; D011188:Potassium