Acidification of Lysosomes and Endosomes

Dyke, Rebecca W. Van

doi:10.1007/978-1-4615-5833-0_10

Cited by 65 publications

(61 citation statements)

References 139 publications

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“…This is achieved by an electrogenic vacuolar H ϩ -ATPase that actively transports protons from the cytosol into the vesicle lumen (11,27,37). Efficient pumping requires charge neutralization by Cl Ϫ flux into the lumen where the steady-state pH depends on the balance of proton pumping, Cl Ϫ permeability, and proton leakage.…”

Section: Discussionmentioning

confidence: 99%

The ClC-3 chloride channel promotes acidification of lysosomes in CHO-K1 and Huh-7 cells

Li¹,

Wang²,

Zhao³

et al. 2002

American Journal of Physiology-Cell Physiology

125

127

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ClC-3 is a voltage-gated Cl−channel that is highly conserved and widely expressed, although its function, localization, and properties remain a matter of considerable debate. In this study, we have shown that heterologous expression of ClC-3 in either Chinese hamster ovary (CHO-K1) or human hepatoma (Huh-7) cells results in the formation of large, acidic vesicular structures within cells. Vesicle formation is prevented by bafilomycin, an inhibitor of the vacuolar ATPase, and is not induced by an E224A mutant of ClC-3 with altered channel activity. This demonstrates that vesicle formation requires both proton pumping and Cl−channel activity. Manipulation of the intracellular Cl−concentration demonstrated that the ClC-3-associated vesicles shrink and swell consistent with a highly Cl−-permeable membrane. The ClC-3 vesicles were identified as lysosomes based on their colocalization with the lysosome-associated proteins lamp-1, lamp-2, and cathepsin D and on their failure to colocalize with fluorescently labeled endosomes. We conclude that ClC-3 is an intracellular channel that conducts Cl− when it is present in intracellular vesicles. Its overexpression results in its appearance in enlarged lysosome-like structures where it contributes to acidification by charge neutralization.

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Section: Discussionmentioning

confidence: 99%

The ClC-3 chloride channel promotes acidification of lysosomes in CHO-K1 and Huh-7 cells

Li¹,

Wang²,

Zhao³

et al. 2002

American Journal of Physiology-Cell Physiology

125

127

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show abstract

“…64 The vesicles are then uncoated by a 70-kDa ATP-dependent enzyme. 65 The vesicle cargo is delivered rapidly to early (or sorting) endosomes that become acidified by ATP-dependent proton pumps 66 (Figure 1). In CHO cells, the pH of the early endosome is B6.0.…”

Section: Clathrin-mediated Endocytosismentioning

confidence: 99%

Intracellular trafficking of nonviral vectors

2005

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“…The progressive acidification of endosomal compartments (from pH 6.0 in early endosomes to pH 4.6-5.0 in lysosomes) because of vacuolar adenosine triphosphatase activity is a well-established phenomenon. [10][11][12][13][14][15][16][17] A major consequence of endosomal acidification is the selective sorting of molecules along the pathways of intracellular transport. The importance of endosomal acidification in regulating a range of biological processes has been well documented in several studies (e.g., the access of certain viruses and toxins into the cytosol after receptor-mediated endocytosis).…”

mentioning

confidence: 99%