title: The position of lysosomes within the cell determines their luminal pH.
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.
authors.affiliation: Program in Cell Biology, Hospital for Sick Children, Toronto, Ontario M5G 0A4, Canada.
authors.forename: Danielle E
authors.initials: DE
authors.lastname: Johnson
authors.affiliation: Program in Cell Biology, Hospital for Sick Children, Toronto, Ontario M5G 0A4, Canada.
authors.forename: Philip
authors.initials: P
authors.lastname: Ostrowski
authors.affiliation: Program in Cell Biology, Hospital for Sick Children, Toronto, Ontario M5G 0A4, Canada.
authors.forename: Valentin
authors.initials: V
authors.lastname: Jaumouillé
authors.affiliation: Program in Cell Biology, Hospital for Sick Children, Toronto, Ontario M5G 0A4, Canada sergio.grinstein@sickkids.ca.
authors.forename: Sergio
authors.initials: S
authors.lastname: Grinstein
mesh_terms: D020727:ADP-Ribosylation Factors / Q000378:metabolism; D048868:Adaptor Proteins, Signal Transducing / Q000378:metabolism; D053898:Biosynthetic Pathways / Q000502:physiology; D045744:Cell Line, Tumor; D006367:HeLa Cells; D006801:Humans; D006863:Hydrogen-Ion Concentration; D008247:Lysosomes / Q000378:metabolism / Q000502:physiology*; D025262:Vacuolar Proton-Translocating ATPases / Q000378:metabolism; D014617:Vacuoles / Q000378:metabolism / Q000502:physiology; D020691:rab GTP-Binding Proteins / Q000378:metabolism; D000090802:rab7 GTP-Binding Proteins
chemical_list: C511801:ARL8B protein, human; D048868:Adaptor Proteins, Signal Transducing; C423317:RILP protein, human; D000090802:rab7 GTP-Binding Proteins; C000716463:rab7 GTP-binding proteins, human; C000594810:ATP6V1G1 protein, human; D025262:Vacuolar Proton-Translocating ATPases; D020727:ADP-Ribosylation Factors; D020691:rab GTP-Binding Proteins