The position of lysosomes within the cell determines their luminal pH
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TLDR
Analysis of luminal lysosomal pH in combination with heterologous expression of lysOSomal-associated proteins indicates that peripheralLysosomes are more alkaline than juxtanuclear ones and that depletion of Rab7 and its effector, RILP, are associated with and can account for the reduced acidification.Abstract:
We examined the luminal pH of individual lysosomes using quantitative ratiometric fluorescence microscopy and report an unappreciated heterogeneity: peripheral lysosomes are less acidic than juxtanuclear ones despite their comparable buffering capacity. An increased passive (leak) permeability to protons, together with reduced vacuolar H(+)-adenosine triphosphatase (V-ATPase) activity, accounts for the reduced acidifying ability of peripheral lysosomes. The altered composition of peripheral lysosomes is due, at least in part, to more limited access to material exported by the biosynthetic pathway. The balance between Rab7 and Arl8b determines the subcellular localization of lysosomes; more peripheral lysosomes have reduced Rab7 density. This in turn results in decreased recruitment of Rab-interacting lysosomal protein (RILP), an effector that regulates the recruitment and stability of the V1G1 component of the lysosomal V-ATPase. Deliberate margination of lysosomes is associated with reduced acidification and impaired proteolytic activity. The heterogeneity in lysosomal pH may be an indication of a broader functional versatility.read more
Citations
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Lysosomes as dynamic regulators of cell and organismal homeostasis
TL;DR: The modulation of lysosome function could be a promising therapeutic strategy for the treatment of cancer as well as metabolic and neurodegenerative disorders.
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V‐ATPase Interacts with ARNO and Arf6 in Early Endosomes and Regulates the Protein Degradative Pathway
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TL;DR: In this paper, the authors demonstrate that the recruitment of the small GTPase Arf6 and ARNO from cytosol to endosomal membranes is driven by V-ATPase-dependent intra-endosomal acidification.
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References
More filters
Journal ArticleDOI
TFEB links autophagy to lysosomal biogenesis.
Carmine Settembre,Chiara Di Malta,Vinicia Assunta Polito,Vinicia Assunta Polito,Moises Garcia Arencibia,Francesco Vetrini,Serkan Erdin,Serkan Erdin,Serpil Uckac Erdin,Serpil Uckac Erdin,Tuong Huynh,Tuong Huynh,Diego L. Medina,Pasqualina Colella,Marco Sardiello,Marco Sardiello,David C. Rubinsztein,Andrea Ballabio +17 more
TL;DR: A mitogen-activated protein kinase–dependent mechanism regulates autophagy by controlling the biogenesis and partnership of two distinct cellular organelles during starvation.
Journal ArticleDOI
Intracellular pH measurements in Ehrlich ascites tumor cells utilizing spectroscopic probes generated in situ.
Journal ArticleDOI
Fluorescence probe measurement of the intralysosomal pH in living cells and the perturbation of pH by various agents
Shoji Ohkuma,Brian Poole +1 more
TL;DR: The results provide evidence for the existence of an active proton accumulation mechanism in the lysosomal membrane and support the theory of lysOSomal accumulation of weak bases by proton trapping.
Journal ArticleDOI
Acidification of the endocytic and exocytic pathways
TL;DR: The Exocytic Pathway and the CharacTERISTICS of PROTON ATPases are reviewed.