Loss of membrane cholesterol influences lysosomal permeability to potassium ions and protons.
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.
Deng
Dong
D
School of Life Sciences, Northeast Normal University, Changchun 130024, PR China.
Jiang
Nan
N
Hao
Shu-Jing
SJ
Sun
Hui
H
Zhang
Guo-jiang
GJ
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
D007477:Ions; D047392:beta-Cyclodextrins; C108732:methyl-beta-cyclodextrin; D002784:Cholesterol; D011188:Potassium