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Molecular mechanisms of endolysosomal Ca2+ signalling in health and disease

Morgan, Anthony J., Platt, Frances M., Lloyd-Evans, Emyr, Galione, Antony·2011·Biochemical Journal

Abstract

Endosomes, lysosomes and lysosome-related organelles are emerging as important Ca2+ storage cellular compartments with a central role in intracellular Ca2+ signalling. Endocytosis at the plasma membrane forms endosomal vesicles which mature to late endosomes and culminate in lysosomal biogenesis. During this process, acquisition of different ion channels and transporters progressively changes the endolysosomal luminal ionic environment (e.g. pH and Ca2+) to regulate enzyme activities, membrane fusion/fission and organellar ion fluxes, and defects in these can result in disease. In the present review we focus on the physiology of the inter-related transport mechanisms of Ca2+ and H+ across endolysosomal membranes. In particular, we discuss the role of the Ca2+-mobilizing messenger NAADP (nicotinic acid adenine dinucleotide phosphate) as a major regulator of Ca2+ release from endolysosomes, and the recent discovery of an endolysosomal channel family, the TPCs (two-pore channels), as its principal intracellular targets. Recent molecular studies of endolysosomal Ca2+ physiology and its regulation by NAADP-gated TPCs are providing exciting new insights into the mechanisms of Ca2+-signal initiation that control a wide range of cellular processes and play a role in disease. These developments underscore a new central role for the endolysosomal system in cellular Ca2+ regulation and signalling.

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Metadata

Authors
Morgan, A. J., Platt, F. M., Lloyd-Evans, E., & Galione, A.
Venue
Biochemical Journal
Published
2011-10-13
Volume
439
Issue
3
Pages
349-378
ISSN
  • 0264-6021 (ISSN-L)
  • 1470-8728
OpenAlex
W1782667879
Cited by
399
References
17
FWCI
13.93
Type
journal article
Language
en
Open access
closed

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CoChat. (2026). Citation check: Molecular mechanisms of endolysosomal Ca2+ signalling in health and disease. https://app.cochat.ai/papers/10.1042/bj20110949
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Morgan, A. J., Platt, F. M., Lloyd-Evans, E., & Galione, A. (2011). Molecular mechanisms of endolysosomal Ca2+ signalling in health and disease. Biochemical Journal. https://doi.org/10.1042/bj20110949

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Contains information from the Semantic Scholar Academic Graph Datasets, made available under the ODC Attribution License (ODC-BY 1.0).

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