Abstract
A distinct set of channels and transporters regulates the ion fluxes across the lysosomal membrane. Malfunctioning of these transport proteins and the resulting ionic imbalance is involved in various human diseases, such as lysosomal storage disorders, cancer, as well as metabolic and neurodegenerative diseases. As a consequence, these proteins have stimulated strong interest for their suitability as possible drug targets. A detailed functional characterization of many lysosomal channels and transporters is lacking, mainly due to technical difficulties in applying the standard patch-clamp technique to these small intracellular compartments. In this review, we focus on current methods used to unravel the functional properties of lysosomal ion channels and transporters, stressing their advantages and disadvantages and evaluating their fields of applicability.
Highlights
Lysosomes are acidic organelles, pH of about 4.6 [1], considered as the digestive system of the animal cell
As a result of these experiments performed on isolated lysosomes, by using concentrative 36Cl− uptake combined with fluorescence measurements of proton fluxes, the authors could establish that the lysosomal transport of Cl− and H+ is mediated by a Cl−/H+ antiporter, identified as CLC-7 [15]
In line with similarity discussed above in trafficking and targeting between tonoplast and lysosomal membrane proteins, mutants plants from Arabidopsis thaliana lacking specific endogenous vacuolar channels or transporters can be used for the expression of the respective homologous animal lysosomal proteins
Summary
PH of about 4.6 [1], considered as the digestive system of the animal cell. Lysosomes are engaged in cross-talk with each other, with other organelles like mitochondria [10] and with proteins/receptors outside the organelle, highlighting the existence of complex cellular mechanisms of regulation. Supporting their vital role, the correct function of these organelles is disturbed in a group of human pathologies known as lysosomal storage disorders, LSDs [11]. Current research on LTPs provides the basis for a better understanding of LSDs and future therapeutic intervention. Besides their involvement in protein degradation and storage functions, lysosome channels are potentially essential for viral infections in humans [13,14]
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