Abstract
Acid assists digestion. That this is true at the subcellular as well as the organismal level was recognized more than 90 years ago by Metchnikoff (1893), who observed that blue litmus turned red when engulfed by protozoans. Today it is universally recognized that lysosomes, the intracellular digestive organelles, show an internal pH approximately 2 units below that of their environment. This not only provides favorable conditions for the activity of lysosomal enzymes, which have acidic pH optima, but also assists directly in the digestive process by denaturing ingested proteins to make them more susceptible to enzymatic proteolysis. In other organelles, internal acidification serves a variety of more subtle purposes. The dissociation of ligands from their receptors in endosomes, the accumulation of catecholamines in storage granules, and the processing and sorting of newly synthesized proteins in the Golgi are processes that are regulated in part by intraorganellar acidity. The transmembrane pH gradient in these organelles is generated and maintained by an ATP-dependent proton pump residing in the organellar membrane. This chapter summarizes the evidence for, and the characteristics of, the proton pump found in lysosomes.
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References
Dell’Antone, P., 1979, Evidence for an ATP-driven “proton pump” in rat liver lysosomes by basic dyes uptake, Biochem. Biophys. Res. Commun. 86:180–189.
Flatmark, T., Gronberg, M., Husebye, E., Jr., and Berge, S. V., 1982, Inhibition by N-ethyimaleimide of the Mg-ATP-driven proton pump of the chromaffin granules, FEBS Lett. 149:71–74
Glickman, J., Croen, K., Kelly, S., and Al-Awqati, Q., 1983, Golgi membranes contain an electrogenic H+ pump in parallel to a chloride conductance, J. CellBiol. 97:1303–1308.
Goldman, R., and Kaplan, A., 1973, Rupture of rat liver lysosomes mediated by L-amino acid esters, Biochim. Biophys. Acta 318:205–216.
Goldman, R., and Rottenberg, H., 1973, Ion distribution in lysosomal suspensions, FEBS Lett. 33:233–238.
Harikumar, P., and Reeves, J. P., 1983, The lysosomal proton pump is electrogenic, J. Biol Chem. 258:10403–10410.
Harikumar, P., and Reeves, J. P., 1984, The lysosomal proton pump, Biochem. Soc. Trans. 12:906–908.
Henning, R., 1975, pH gradient across the lysosomal membrane generated by selective cation permeability and Donnan equilibrium, Biochim. Biophys. Acta. 401:307–316.
Maunsbach, A., 1969, Functions of lysosomes in kidney cells, in: Lysosomes in Biology and Pathology, Vol. 1 (J. T. Dingle and H. R. Fell, eds.), North-Holland, Amsterdam, pp. 115–153.
Maunsbach, A. B., 1974, Isolation of kidney lysosomes. Methods Enzymol. 31A:330–339.
Mego, J. L., 1975, Further evidence for a proton pump in mouse kidney phagolysosomes: Effect of nigericin and 2,4-dinitrophenol on the stimulation of intralysosomal proteolysis by ATP, Biochem. Biophys. Res. Commun. 67:571–575.
Mego, J. L., Farb, R. M., and Barnes, J., 1972, An adenosine triphosphate-dependent stabilization of proteolytic activity in heterolysosomes. Evidence for a proton pump, Biochem. J. 128:763–769.
Merion, M., Schlesinger, P. Brooks, R. M., Moehring, J. M., Moehring, T. J., and Sly, W. S., 1983, Defective acidification of endosomes in Chinese hamster ovary cell mutants “cross-resistant” to toxins and viruses, Proc. Natl. Acad. Sci. U.S.A. 80:5315–5319.
Metchnikoff, E., 1983, Lectures on the Comparative Pathology of Inflammation, Kegan, Paul, Trench, Trübner and Co., London.
Moriyama, Y., Takano, T., and Ohkuma, S., 1982, Acridine orange as a fluorescent probe for lysosomal proton pump, J. Biochem. 92:1333–1336.
Moriyama, Y., Takano, T., and Ohkuma, S., 1984a, Proton translocating ATPase in lysosomal membrane ghosts. Evidence that alkaline Mg2+-ATPase acts as a proton pump, J. Biochem. 95:995–1007.
Moriyama, Y., Takano, T., and Ohkuma, S., 1984b, Solubilization and reconstitution of a lysosomal H+-pump, J. Biochem. 96:927–930.
Ohkuma, S., and Poole, B., 1978, Fluorescence probe measurement of the intralysosomal pH in Uving cells and the perturbation of pH by various agents, Proc. Natl. Acad. Sci. U.S.A. 75:3327–3331.
Ohkuma, S., Moriyama, Y., and Takano, T., 1982, Identification and characterization of a proton pump on lysosomes by fluorescein isothiocyanate dextran fluorescence, Proc. Natl. Acad. Sci. U.S.A. 79:2758–2762.
Ohkuma, S., Moriyama, Y., and Takano, T., 1983, Electrogenic nature of lysosomal proton pump as revealed with a cyanine dye, J. Biochem. 94:1935–1943.
Rees-Jones, R., and Al-Awqati, Q., 1984, Proton-translocating adenosine-triphosphate in rough and smooth microsomes from rat liver. Biochemistry 23:2236–2240.
Reeves, J. P., 1984, The mechanism of lysosomal acidification, in: Lysosomes in Biology and Pathology, Vol. 7 (J. T. Dingle, R. T., Dean, and W. Sly, eds.), Elsevier, Amsterdam, pp. 175–199.
Reeves, J. P., and Reames, T., 1981, ATP stimulates amino acid accumulation by lysosomes incubated with amino acid methyl esters. Evidence for a lysosomal proton pump, J. Biol. Chem. 256:6047–6053.
Reijngoud, D.-J., and Tager, J. M., 1973, Measurement of intralysosomal pH, Biochim. Biophys. Acta. 297:174–178.
Reijngoud, D.-J., and Tager, J. M., 1977, The permeability properties of the lysosomal membrane, Biochim. Biophys. Acta 472:419–449.
Reijngoud, D.-J., Oud, P. S., and Tager, J. M., 1976, Effect of ionophores on intralysosomal pH, Biochim. Biophys. Acta 448:303–313.
Rudnick, G., 1986, Acidification of intracellular organelles: Mechanism and function, in: Physiology of Membrane Disorders, ed. 2 (T. E. Andreoli, D. D. Fanestil, J. P. Hoffman, and S. Schultz, eds.). Plenum Press, New York, 409–422.
Schneider, D. L., 1979, The acidification of rat liver lysosomes in vitro: A role for the membranous ATPase as a proton pump, Biochem. Biophys. Res. Commun. 87:559–565.
Schneider, D. L., 1981, ATP-dependent acidification of intact and disrupted lysosomes. Evidence for an ATP-driven proton pump, J. Biol. Chem. 256:3858–3864.
Schneider, D. L., 1983, ATP-dependent acidification of membrane vesicles isolated from purified rat liver lysosomes. Acidification activity requires phosphate, J. Biol. Chem. 258:1833–1838.
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© 1986 Plenum Press, New York
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Harikumar, P., Reeves, J.P. (1986). The Lysosomal Proton Pump. In: Poste, G., Crooke, S.T. (eds) New Insights into Cell and Membrane Transport Processes. New Horizons in Therapeutics. Springer, Boston, MA. https://doi.org/10.1007/978-1-4684-5062-0_4
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DOI: https://doi.org/10.1007/978-1-4684-5062-0_4
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