Acidification of Lysosomes and Endosomes

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Abstract
In eukaryotic cells the interior space of endosomes, lysosomes, and a variety of other intracellular organelles is maintained at a pH considerably more acidic than either cytosolic pH or extracellular pH. This acidic vesicle interior can be demonstrated by staining of living cells with pH-sensitive dyes such as the fluorescent tertiary amine acridine orange, which is protonated and trapped in low pH compartments. Cells such as hepatocytes that are endocytically active exhibit literally hundreds of fluorescent acid vesicles (Lake et al., 1987). Concomitant exposure of cells to agents that eliminate pH gradients, such as proton ionophores, or high concentrations of other tertiary amines abolishes this fluorescence, confirming the acid nature of these intracellular compartments and illustrating that vesicle acidification is the product of the active transport of protons rather than simply a Donnan-type equilibrium. Considerable experimental work over the past 15 years has elucidated the mechanisms for acidification of intracellular organelles, including lysosomes and endosomes, and current investigative efforts are focused at understanding regulation of the acidification mechanism.

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