Ion flux and the function of endosomes and lysosomes: pH is just the start

Abstract

The ionic nature of endosomes varies considerably in character along the endocytic pathway. Counter-ion flux across the limiting membrane of endosomes has long been considered essential for full acidification and normal endosome/lysosomal function. The proximal functions of luminal ions, however, have been difficult to assess. The recent development of transgenic mice carrying mutations in the intracellular chloride channels (ClCs) has provided a tool to uncouple Cl(-) influx from endosomal acidification. Intriguingly, many of the defects of the endo-lysomal system attributed to aberrant pH persist in the Cl(-)-deficient mice implying a direct regulatory role for Cl(-) influx in endosome function. These observations may begin to explain the abundance of endosomal ion transporters, including ClCs, sodium-proton exchangers, two-pore channels and mucolipins, that have been localized to endo-lysosomes, and the extensive changes in luminal ion composition therein. In this review, we summarize what is known regarding the mediators of endosomal ion flux, and discuss the implications of changing ionic content on endo-lysosomal function.

Anthrax toxin-induced rupture of artificial lipid bilayer membranes

“…97 However, other ions and their transporters lower the potential to (27 ± 16) mV (positive inside) 98 which is consistent with the expected range estimated through the Goldman-Hodgkin-Katz equation 96,97 or from a kinetic analysis of the known channels and transporters in the membranes. 99 If we assume the distribution of the ψ values is Gaussian, then ≈2% of the endosomes will have transmembrane potentials that are sufficiently great (|V| ≥ 70 mV) that would support the putative LF N or EF N translocation model or the membrane rupture model suggested herein (Fig.…”

“…96 If the proton was the only membrane-permeant species at steady state, the transmembrane potential, ψ, could be as large as 195 mV at T = 37…”

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“…Therefore, the loss of Nhx1p activity resulted in a shift in intracellular sodium, potassium, and proton concentrations. However, Nhx1p activity does not noticeably change endosomal or cytosolic Na ϩ and K ϩ concentrations, because of the much higher concentration of Na ϩ or K ϩ than H ϩ in cells (46,47). Thus, we considered the potential importance of pH in MVB formation.…”

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