期刊
PHYSICAL BIOLOGY
卷 20, 期 6, 页码 -出版社
IOP Publishing Ltd
DOI: 10.1088/1478-3975/acfe6a
关键词
calcium; multivesicular; lysosomes; acidic calcium stores; lysobisphosphatidic acid; endosomes; intralumenal
This paper investigates the mechanism of calcium storage in endo-lysosomes as intracellular calcium stores. It is found that the multivesicular ultrastructure and intralumenal membranes of endo-lysosomes contribute to its calcium storage capacity by providing additional bilayer surface.
It is now established that endo-lysosomes, also referred to as late endosomes, serve as intracellular calcium store, in addition to the endoplasmic reticulum. While abundant calcium-binding proteins provide the latter compartment with its calcium storage capacity, essentially nothing is known about the mechanism responsible for calcium storage in endo-lysosomes. In this paper, we propose that the structural organization of endo-lysosomal membranes drives the calcium storage capacity of the compartment. Indeed, endo-lysosomes exhibit a characteristic multivesicular ultrastructure, with intralumenal membranes providing a large amount of additional bilayer surface. We used a theoretical approach to investigate the calcium storage capacity of endosomes, using known calcium binding affinities for bilayers and morphological data on endo-lysosome membrane organization. Finally, we tested our predictions experimentally after Sorting Nexin 3 depletion to decrease the intralumenal membrane content. We conclude that the major negatively-charge lipids and proteins of endo-lysosomes serve as calcium-binding molecules in the acidic calcium stores of mammalian cells, while the large surface area of intralumenal membranes provide the necessary storage capacity.
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