Sensors and regulators of intracellular pH
01 Jan 2010-Nature Reviews Molecular Cell Biology (Nature Publishing Group)-Vol. 11, Iss: 1, pp 50-61
TL;DR: A dynamic, finely tuned balance between proton-extruding andProton-importing processes underlies pH homeostasis not only in the cytosol, but in other cellular compartments as well.
Abstract: Protons dictate the charge and structure of macromolecules and are used as energy currency by eukaryotic cells. The unique function of individual organelles therefore depends on the establishment and stringent maintenance of a distinct pH. This, in turn, requires a means to sense the prevailing pH and to respond to deviations from the norm with effective mechanisms to transport, produce or consume proton equivalents. A dynamic, finely tuned balance between proton-extruding and proton-importing processes underlies pH homeostasis not only in the cytosol, but in other cellular compartments as well.
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TL;DR: How recent insights into the structure and function of key molecules and their regulators reveal novel strategies of bacterial pH homeostasis may help to target certain pathogens more accurately and to harness the capacities of environmental bacteria more efficiently is described.
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703 citations
References
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TL;DR: "It is certain that all bodies whatsoever, though they have no sense, yet they have perception, and whether the body be alterant or alterec, evermore a perception precedeth operation; for else all bodies would be like one to another."
8,157 citations
"Sensors and regulators of intracell..." refers background in this paper
...Instead, it has been proposed that the kinetic data best fit a Monod–Wyman–Changeux mode...
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TL;DR: The acidity of intracellular compartments and the extracellular environment is crucial to various cellular processes, including membrane trafficking, protein degradation, bone resorption and sperm maturation, and the V-ATPases represent attractive and potentially highly specific drug targets.
Abstract: The acidity of intracellular compartments and the extracellular environment is crucial to various cellular processes, including membrane trafficking, protein degradation, bone resorption and sperm maturation. At the heart of regulating acidity are the vacuolar (V-)ATPases--large, multisubunit complexes that function as ATP-driven proton pumps. Their activity is controlled by regulating the assembly of the V-ATPase complex or by the dynamic regulation of V-ATPase expression on membrane surfaces. The V-ATPases have been implicated in a number of diseases and, coupled with their complex isoform composition, represent attractive and potentially highly specific drug targets.
1,355 citations
"Sensors and regulators of intracell..." refers background in this paper
...These cells express on their surface vacuolar-type (V) electrogenic H + -ATP hydrolases (V-ATPases) — energy-driven active proton pumps that are similar to those found in endomembranes (see below) and are characteristically sensitive to macrolide antibiotics such as bafilomyci...
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TL;DR: Ce rapport de synthese tente de fournir une vue generale sur les relations possibles qui existent entre les effets du Ca 2+ a l'interieur des mitochondries and le besoin d'ATP reclame par les cellules des vertebres.
Abstract: Ce rapport de synthese tente de fournir une vue generale sur les relations possibles qui existent entre les effets du Ca 2+ a l'interieur des mitochondries et le besoin d'ATP reclame par les cellules des vertebres
1,344 citations
TL;DR: The pH of the medial/trans-Golgi was measured and demonstrated that the Golgi membrane in intact cells is relatively permeable to H+, and that Cl- serves as a counter-ion for H+ transport and likely helps to maintain electroneutrality.
Abstract: Many cellular events depend on a tightly compartmentalized distribution of H+ ions across membrane-bound organelles. However, measurements of organelle pH in living cells have been scarce. Several mutants of the Aequorea victoria green fluorescent protein (GFP) displayed a pH-dependent absorbance and fluorescent emission, with apparent pKa values ranging from 6.15 (mutations F64L/S65T/H231L) and 6.4 (K26R/F64L/S65T/Y66W/N146I/M153T/V163A/N164H/H231L) to a remarkable 7.1 (S65G/S72A/T203Y/H231L). We have targeted these GFPs to the cytosol plus nucleus, the medial/trans-Golgi by fusion with galactosyltransferase, and the mitochondrial matrix by using the targeting signal from subunit IV of cytochrome c oxidase. Cells in culture transfected with these cDNAs displayed the expected subcellular localization by light and electron microscopy and reported local pH that was calibrated in situ with ionophores. We monitored cytosolic and nuclear pH of HeLa cells, and mitochondrial matrix pH in HeLa cells and in rat neonatal cardiomyocytes. The pH of the medial/trans-Golgi was measured at steady-state (calibrated to be 6.58 in HeLa cells) and after various manipulations. These demonstrated that the Golgi membrane in intact cells is relatively permeable to H+, and that Cl− serves as a counter-ion for H+ transport and likely helps to maintain electroneutrality. The amenability to engineer GFPs to specific subcellular locations or tissue targets using gene fusion and transfer techniques should allow us to examine pH at sites previously inaccessible.
1,087 citations
"Sensors and regulators of intracell..." refers background in this paper
...0) owing to H + extrusion across the inner membrane by components of the electron transport chai...
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TL;DR: The mitochondria are tuned to oscillating [Ca2+]c signals, the frequency of which can control the CSMDHs over the full range of potential activities.
1,054 citations
"Sensors and regulators of intracell..." refers background in this paper
..., and has been proposed as a means of synchronizing energy production with cellular need...
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