scholarly journals Mitochondrial uncouplers inhibit clathrin-mediated endocytosis largely through cytoplasmic acidification

2016 ◽  
Vol 7 (1) ◽  
Author(s):  
Wim Dejonghe ◽  
Sabine Kuenen ◽  
Evelien Mylle ◽  
Mina Vasileva ◽  
Olivier Keech ◽  
...  
Keyword(s):  
Cytoplasmic Acidification ◽  
Mitochondrial Uncouplers

Cytoplasmic pH regulation in phorbol ester-activated human neutrophils

1986 ◽  
Vol 251 (1) ◽  
pp. C55-C65 ◽  
Author(s):  
S. Grinstein ◽  
W. Furuya
Keyword(s):  
Metabolic Pathways ◽  
Phorbol Esters ◽  
Ph Regulation ◽  
Human Neutrophils ◽  
Hexose Monophosphate ◽  
Cytoplasmic Ph ◽  
Extracellular Acidification ◽  
Hexose Monophosphate Shunt ◽  
Activated Neutrophils ◽  
Cytoplasmic Acidification

Activation of neutrophils by 12-O-tetradecanoylphorbol-13-acetate (TPA) is accompanied by an initial cytoplasmic acidification, followed by an alkalinizing phase due to Na+-H+ countertransport. The source of the acidification, which is fully expressed by activation with TPA in Na+-free or amiloride-containing media, was investigated. The acidification phase was detected also in degranulated and enucleated cytoplasts, ruling out a major contribution by the nucleus or secretory vesicles. Cytoplasmic acidification was found to be associated with an extracellular acidification, suggesting metabolic generation of H+. Two principal metabolic pathways are stimulated in activated neutrophils: the reduction of O2 by NADPH-oxidase and the hexose monophosphate shunt. A good correlation was found between the activity of these pathways and the changes in cytoplasmic pH. Inhibition of superoxide synthesis prevented the TPA-induced cytoplasmic acidification. Moreover, activation of the hexose monophosphate shunt with permeable NADPH-oxidizing agents (in the absence of TPA) also produced a cytoplasmic acidification. Cytoplasmic acidification was also elicited by exogenous diacylglycerol and by other beta-phorbol diesters, which are activators of the kinase, but not by unesterified phorbol or by alpha-phorbol diesters, which are biologically inactive. The results suggest that the cytoplasmic acidification induced by phorbol esters in neutrophils reflects accumulation of H+ liberated during the metabolic burst that follows activation.

scholarly journals Exploring the therapeutic potential of mitochondrial uncouplers in cancer

2021 ◽  
pp. 101222
Author(s):  
Riya Shrestha ◽  
Edward Johnson ◽  
Frances L. Byrne
Keyword(s):  
Therapeutic Potential ◽  
Mitochondrial Uncouplers

scholarly journals Trialkyl(vinyl)phosphonium Chlorophenol Derivatives as Potent Mitochondrial Uncouplers and Antibacterial Agents

ACS Omega ◽  
2021 ◽  
Author(s):  
Natalia V. Terekhova ◽  
Lyudmila S. Khailova ◽  
Tatyana I. Rokitskaya ◽  
Pavel A. Nazarov ◽  
Daut R. Islamov ◽  
...  
Keyword(s):  
Antibacterial Agents ◽  
Mitochondrial Uncouplers

scholarly journals Effects of cytoplasmic acidification on clathrin lattice morphology.

1989 ◽  
Vol 108 (2) ◽  
pp. 401-411 ◽  
Author(s):  
J Heuser
Keyword(s):  
Plasma Membrane ◽  
Cultured Cells ◽  
Membrane Receptors ◽  
The Other ◽  
Culture Dish ◽  
Initial Curvature ◽  
Internal Ph ◽  
Cytoplasmic Acidification

Reducing the internal pH of cultured cells by several different protocols that block endocytosis is found to alter the structure of clathrin lattices on the inside of the plasma membrane. Lattices curve inward until they become almost spherical yet remain stubbornly attached to the membrane. Also, the lattices bloom empty "microcages" of clathrin around their edges. Correspondingly, broken-open cells bathed in acidified media demonstrate similar changes in clathrin lattices. Acidification accentuates the normal tendency of lattices to round up in vitro and also stimulates them to nucleate microcage formation from pure solutions of clathrin. On the other hand, several conditions that also inhibit endocytosis have been found to create, instead of unusually curved clathrin lattices with extraneous microcages, a preponderance of unusually flat lattices. These treatments include pH-"clamping" cells at neutrality with nigericin, swelling cells with hypotonic media, and sticking cells to the surface of a culture dish with soluble polylysine. Again, the unusually flat lattices in such cells display a tendency to round up and to nucleate clathrin microcage formation during subsequent in vitro acidification. This indicates that regardless of the initial curvature of clathrin lattices, they all display an ability to grow and increase their curvature in vitro, and this is enhanced by lowering ambient pH. Possibly, clathrin lattice growth and curvature in vivo may also be stimulated by a local drop in pH around clusters of membrane receptors.

Cytoplasmic acidification is not an effector mechanism of VP16 or DEX-induced apoptosis in CEM T leukaemia cells

1999 ◽  
Vol 112 (11) ◽  
pp. 1755-1760
Author(s):  
R.S. Benson ◽  
C. Dive ◽  
A.J. Watson
Keyword(s):  
Chromatin Condensation ◽  
Parp Cleavage ◽  
Intracellular Acidification ◽  
Over Expression ◽  
Effector Phase ◽  
Execution Phase ◽  
Cytoplasmic Acidification ◽  
Physiological Values ◽  
Induced Apoptosis

The role of intracellular acidification in the execution phase of apoptosis is not well understood. Here we examine the effect of Bcl-2 over-expression on intracellular acidification occurring during apoptosis. We found, that in CEM cells, neither DEX nor VP16-induced apoptosis lead to a significant change in intracellular pH (pHi). Furthermore, we found that shifting pHi away from physiological values was unable to induce chromatin condensation or poly(ADP-ribose) polymerase (PARP) cleavage in the presence of Bcl-2 over-expression. However, it was found that maximum chromatin condensation and PARP cleavage occurred at near physiological pHi values. Taken together these data suggest that intracellular acidification does not trigger the effector phase of CEM apoptosis.

scholarly journals Effect of Low-pressure Carbonation on the Heat Inactivation and Cytoplasmic Acidification of Saccharomyces cerevisiae

2012 ◽  
Vol 2 (12) ◽  
Author(s):  
Wannaporn Klangpetch ◽  
Tomoe Nakai ◽  
Kei Nishiyama ◽  
Seiji Noma ◽  
Noriyuki Igura ◽  
...  
Keyword(s):  
Saccharomyces Cerevisiae ◽  
Low Pressure ◽  
Heat Inactivation ◽  
Cytoplasmic Acidification

Oxygen and Light Accelerate Recovery from SO2-induced Inhibition of Leaf Photosynthesis and from Cytoplasmic Acidification

2000 ◽  
Vol 156 (4) ◽  
pp. 537-544 ◽  
Author(s):  
Katja Hüve ◽  
Sonja Veljovic-Jovanovic ◽  
Christian Wiese ◽  
Ulrich Heber
Keyword(s):  
Leaf Photosynthesis ◽  
Cytoplasmic Acidification

scholarly journals Selective interactions among the multiple connexin proteins expressed in the vertebrate lens: the second extracellular domain is a determinant of compatibility between connexins.

1994 ◽  
Vol 125 (4) ◽  
pp. 879-892 ◽  
Author(s):  
T W White ◽  
R Bruzzone ◽  
S Wolfram ◽  
D L Paul ◽  
D A Goodenough
Keyword(s):  
Extracellular Domain ◽  
Adjacent Cell ◽  
Molecular Determinants ◽  
Voltage Dependent ◽  
Cytoplasmic Acidification ◽  
Intercellular Channels ◽  
Connexin Proteins ◽  
Heterotypic Channels ◽  
Selective Process ◽  
High Conductance

Gap junctions are collections of intercellular channels composed of structural proteins called connexins (Cx). We have examined the functional interactions of the three rodent connexins present in the lens, Cx43, Cx46, and Cx50, by expressing them in paired Xenopus oocytes. Homotypic channels containing Cx43, Cx46, or Cx50 all developed high conductance. heterotypic channels composed of Cx46 paired with either Cx43 or Cx50 were also well coupled, whereas Cx50 did not form functional channels with Cx43. We also examined the functional response of homotypic and heterotypic channels to transjunctional voltage and cytoplasmic acidification. We show that all lens connexins exhibited sensitivity to cytoplasmic acidification as well as to voltage, and that voltage-dependent closure of heterotypic channels for a given connexin was dramatically influenced by its partner connexins in the adjacent cell. Based on the observation that Cx43 can discriminate between Cx46 and Cx50, we investigated the molecular determinants that specify compatibility by constructing chimeric connexins from portions of Cx46 and Cx50 and testing them for their ability to form channels with Cx43. When the second extracellular (E2) domain in Cx46 was replaced with the E2 of Cx50, the resulting chimera could no longer form heterotypic channels with Cx43. A reciprocal chimera, where the E2 of Cx46 was inserted into Cx50, acquired the ability to functionally interact with Cx43. Together, these results demonstrate that formation of intercellular channels is a selective process dependent on the identity of the connexins expressed in adjacent cells, and that the second extracellular domain is a determinant of heterotypic compatibility between connexins.

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