scholarly journals A cation counterflux supports lysosomal acidification

2010 ◽  
Vol 189 (7) ◽  
pp. 1171-1186 ◽  
Author(s):  
Benjamin E. Steinberg ◽  
Kassidy K. Huynh ◽  
Alexandre Brodovitch ◽  
Sabrina Jabs ◽  
Tobias Stauber ◽  
...  

The profound luminal acidification essential for the degradative function of lysosomes requires a counter-ion flux to dissipate an opposing voltage that would prohibit proton accumulation. It has generally been assumed that a parallel anion influx is the main or only counter-ion transport that enables acidification. Indeed, defective anion conductance has been suggested as the mechanism underlying attenuated lysosome acidification in cells deficient in CFTR or ClC-7. To assess the individual contribution of counter-ions to acidification, we devised means of reversibly and separately permeabilizing the plasma and lysosomal membranes to dialyze the cytosol and lysosome lumen in intact cells, while ratiometrically monitoring lysosomal pH. Replacement of cytosolic Cl− with impermeant anions did not significantly alter proton pumping, while the presence of permeant cations in the lysosomal lumen supported acidification. Accordingly, the lysosomes were found to acidify to the same pH in both CFTR- and ClC-7–deficient cells. We conclude that cations, in addition to chloride, can support lysosomal acidification and defects in lysosomal anion conductance cannot explain the impaired microbicidal capacity of CF phagocytes.

2008 ◽  
Vol 31 (4) ◽  
pp. 23
Author(s):  
Benjamin E Steinberg ◽  
Alexandre Brodovitch ◽  
Kassidy K Huynh ◽  
Sergio Grinstein

Background: Lysosome acidification is the result of proton pumping by thevacuolar-type ATPase (V-ATPase). Because the V-ATPase is electrogenic, a substantial lysosomal membrane potential can develop if left uncompensated by counterions. An increasing membrane potential will oppose further proton pumping, limiting the acidification. It has generally been assumed that a parallel anion influx accompanies proton pumping to enable acidification. Indeed, defective anion channel function in cystic fibrosis (CF) has been suggested as the mechanism underlying attenuated lysosomal acidification and impaired microbial killing in the lung (Di A, et al., 2006, Nature Cell Biol. 8, 933-944). Chronic lung inflammation and infection represent the major source of morbidity and mortality in CF, and understanding the mechanism underlying the disease will therefore have far-reaching therapeutic implications. As such, it is important to accurately evaluate the reported role of CFTR in lysosome acidification. Methods: To assess the individual contribution of counterions to acidification, we carried out cytosolic and lysosomal ion substitution experiments in intact cells while monitoring lysosomal pH by ratiometric imaging. Results: Replacement of cytosolic Cl^- with impermeant anions did not alter the rate or extent of proton pumping. In contrast, permeant luminalcations were required for normal acidification. Because cations are the main counterion for lysosomal proton uptake, defects in the lysosomal pH are not anticipated in CF cells. Accordingly, the lysosomes of CFTR-deficient alveolar macrophages were found to acidify normally. Conclusion: We conclude that cations are the primary counterions responsible for lysosomal acidification and that defects in lysosomal anion conductance cannot explain the impaired microbicidal capacity of CF phagocytes.


2004 ◽  
Vol 57 (12) ◽  
pp. 1211 ◽  
Author(s):  
Luboš Vrbka ◽  
Pavel Jungwirth

Aqueous solvation of tetrabutylammonium fluoride and iodide was investigated by means of molecular dynamics simulations in extended slab geometry. The varying propensities of the individual ions for the air/water interface were quantified and analyzed in terms of hydrophobic, polarization, and ion–ion interactions. While the cations behave as standard ionic surfactants, the surface behaviour of the halide counter ions strongly depends on the ionic size and polarizability—iodide is surface active, while fluoride is repelled from the interface. The counter-ion effects at different concentrations on the density and charge profiles across the aqueous slab are discussed in detail.


eLife ◽  
2014 ◽  
Vol 3 ◽  
Author(s):  
Sarina Ravens ◽  
Marjorie Fournier ◽  
Tao Ye ◽  
Matthieu Stierle ◽  
Doulaye Dembele ◽  
...  

The histone acetyltransferase (HAT) Mof is essential for mouse embryonic stem cell (mESC) pluripotency and early development. Mof is the enzymatic subunit of two different HAT complexes, MSL and NSL. The individual contribution of MSL and NSL to transcription regulation in mESCs is not well understood. Our genome-wide analysis show that i) MSL and NSL bind to specific and common sets of expressed genes, ii) NSL binds exclusively at promoters, iii) while MSL binds in gene bodies. Nsl1 regulates proliferation and cellular homeostasis of mESCs. MSL is the main HAT acetylating H4K16 in mESCs, is enriched at many mESC-specific and bivalent genes. MSL is important to keep a subset of bivalent genes silent in mESCs, while developmental genes require MSL for expression during differentiation. Thus, NSL and MSL HAT complexes differentially regulate specific sets of expressed genes in mESCs and during differentiation.


OENO One ◽  
1999 ◽  
Vol 33 (4) ◽  
pp. 195
Author(s):  
Claudio Delfini ◽  
Chiara Cocito ◽  
M. Bonino

<p style="text-align: justify;">There are evidences that a grape must of a non aromatic vine, not having perfume and revealing by gaschromatographie only some classes of compounds common to the musts of all the vine varieties, can originate a pool of characterizing fragrant substances after contact with the yeast during fermentation. Therefore, despite the scarce scientific knowledge available on biochemical mechanisms involved in <em>Saccharomyces cerevisiae</em> in the formation of a wine aromatic pattern, it can be likely hypothesized that the yeast could be the biological motor of this aromatic transformation. The yeast can act on the compounds of the must with many periplasmic enzymes (estérases, glycosidases, lyases, lipases, proteases, peptidases, pectolytiques) and several are the scientific contributions underlining the existence of an interaction between the yeast and the vine variety in the formation of wine aromatic characteristics. Besides the individual contribution of substances sensorially active, the yeast would contribute to the transformation of unknown varietal aromatic precursors that are in the grape skins and/or musts. The biochemical, genetic and physiological aspects of this transformation still have to be understood. At the end, we have to answer some important questions such as the mutual role that grape and/or yeast enzymes have during and soon after crushing in the liberation of the varietal precursors and in the conversion of these in fragrant compounds.</p>


2019 ◽  
Vol 21 (8) ◽  
pp. 4461-4471 ◽  
Author(s):  
Marvin Asido ◽  
Peter Eberhardt ◽  
Clara Nassrin Kriebel ◽  
Markus Braun ◽  
Clemens Glaubitz ◽  
...  

We report a comparative study on the structural dynamics of the light-driven sodium pump Krokinobacter eikastus rhodopsin 2 wild type under sodium and proton pumping conditions by means of time-resolved IR spectroscopy.


2022 ◽  
pp. 540-577
Author(s):  
Gustavo Marques da Costa ◽  
Darlan Daniel Alves ◽  
Danielle Paula Martins ◽  
Katiucia Nascimento Adam ◽  
Sabrina Antunes Vieira ◽  
...  

The objective of this chapter is to present the central concepts, parameters, and methods for the monitoring of climate changes, with a focus on air pollution, and the possible global and regional impacts of climate changes as well. There are plant species used as bioindicators that have a high sensitivity or ability to accumulate environmental pollutants. Another method that this chapter will present is the use of receiver models that employ both mathematical and statistical approaches to quantify the individual contribution of a given number of emission sources in the composition of a sample. The data presented in this chapter will provide reliable bases and methodologies for environmental control, supporting the adoption of more restrictive policies.


2017 ◽  
Vol 20 ◽  
pp. S120
Author(s):  
Angus Pike ◽  
Kane Middleton ◽  
Catriona B. Burdon ◽  
Mark Jaffrey ◽  
Herbert Groeller

1998 ◽  
Vol 334 (3) ◽  
pp. 731-741 ◽  
Author(s):  
Shoji OHKUMA ◽  
Tomohiko SATO ◽  
Masayuki OKAMOTO ◽  
Hidekazu MATSUYA ◽  
Kunizo ARAI ◽  
...  

We reported previously [Kataoka, Muroi, Ohkuma, Waritani, Magae, Takatsuki, Kondo, Yamasaki and Nagai (1995) FEBS Lett. 359, 53–59] that prodigiosin 25-C (one of the red pigments of the prodigiosin group produced by micro-organisms like Streptomycesand Serratia) uncoupled vacuolar H+-ATPase, inhibited vacuolar acidification and affected glycoprotein processing. In the present study we show that prodigiosin, metacycloprodigiosin and prodigiosin 25-C, all raise intralysosomal pH through inhibition of lysosomal acidification driven by vacuolar-type (V-)ATPase without inhibiting ATP hydrolysis in a dose-dependent manner with IC50 values of 30–120 pmol/mg of protein. The inhibition against lysosomal acidification was quick and reversible, showing kinetics of simple non-competitive (for ATP) inhibition. However, the prodigiosins neither raised the internal pH of isolated lysosomes nor showed ionophoric activity against H+ or K+ at concentrations where they strongly inhibited lysosomal acidification. They required Cl- for their acidification inhibitory activity even when driven in the presence of K+ and valinomycin, suggesting that their target is not anion (chloride) channel(s). In fact, the prodigiosins inhibited acidification of proteoliposomes devoid of anion channels that were reconstituted from lysosomal vacuolar-type (V-)ATPase and Escherichia coli phospholipids. However, they did not inhibit the formation of an inside-positive membrane potential driven by lysosomal V-ATPase. Instead, they caused quick reversal of acidified pH driven by lysosomal V-ATPase and, in acidic buffer, produced quick acidification of lysosomal pH, both only in the presence of Cl-. In addition, they induced swelling of liposomes and erythrocytes in iso-osmotic ammonium salt of chloride but not of gluconate, suggesting the promotion of Cl- entry by prodigiosins. These results suggest that prodigiosins facilitate the symport of H+ with Cl- (or exchange of OH- with Cl-) through lysosomal membranes, resulting in uncoupling of vacuolar H+-ATPase.


2020 ◽  
Vol 302 (5) ◽  
pp. 1167-1167
Author(s):  
Reut Rotem ◽  
Misgav Rottenstreich ◽  
Ella Prado ◽  
Yael Baumfeld ◽  
David Yohay ◽  
...  

2013 ◽  
Vol 3 (3) ◽  
pp. 291-296
Author(s):  
K. Oulmi ◽  
K. E. Bouhidel ◽  
G. M. Andreadis

The present work investigates the effect of the counter ion nature on the noise of the over-limiting current (Iov). Moreover, the electrochemical methods, current voltage curve (I–V) and the chronopotentiometry (V–t) measurements are applied. The over-limiting current is always accompanied by a neat electrical noise. It is a well accepted experimental phenomenon. The study of this noise may contribute to a better understanding of the Iov and the feasibility of electrodialysis operation at this current in terms of energy consumption. The electrical noise depends directly on the counter ion nature. The power spectral density of the membrane's potential fluctuation was obtained via Fourier analysis of the time series recorded during the transport of counter ions (K+ and NH4+). The spectra are evaluated above the limiting current indicating the differences between the K+ and the NH4+. It is found that the cation NH4+ presents a singular behaviour and the noise is minimal.


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