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PubMed1983

On the mechanism by which Mg2+ and adenine nucleotides restore membrane potential in rat liver mitochondria deenergized by Ca2+ and phosphate.

The presence of ATP or ADP in the incubation medium prevents the collapse of membrane potential induced by external Ca2+ and phosphate. The same adenine nucleotides are unable to restore collapsed membrane potential unless Mg2+ are also added. Bongkrekate is also able to prevent the effects of external Ca2+ and phosphate and when added after membrane potential has collapsed strongly potentiates the restorative action of ATP or ADP. Atractyloside has an opposite effect.

Adenine Nucleotides↗
PubMed1993

Tissue specificity of the regulation of ATP hydrolysis by isolated plant mitochondria.

Pea leaf mitochondria had a high ATP hydrolase activity following the collapse of the membrane potential by addition of valinomycin in state 4. In mitochondria isolated from potato tubers such ATP hydrolase activity was not observed. Pea leaf mitochondria also had a delta pH, in contrast to what was previously found for potato tuber mitochondria. This delta pH could, however, not explain the different results on ATP hydrolysis since this activity was also observed in the presence of nigericin. The results suggest a tissue-specific regulation of ATP hydrolysis in resting organs (potato tubers) as compared to active organs (leaves).

Adenosine Triphosphate↗
PubMed1997

Potassium collapses the deltaP in yeast mitochondria while the rate of ATP synthesis is inhibited only partially: modulation by phosphate.

Addition of increasing concentrations of K+ to yeast mitochondria in the presence of 0 to 400 microM phosphate and 200 microM Mg2+ led to uncoupled respiration and decreased protonmotive force (deltaP):at 0 K+ deltaP = 213 mV, negative inside, where deltapsi = 180 mV and deltapH = 33 mV, while at 20 mM K+ deltaP = 28 mV, where deltapsi = 16 mV and deltapH = 12 mV. In contrast, the synthesis of ATP resulted in smaller values for the Km and the Vmax in 400 microM Pi and increasing ADP: in 0 K+, Km = 18.6 microM and Vmax = 75.4 nmol (min x mg protein)-1, while in 20 mM K+, Km = 5.2 microM and Vmax = 46.0 nmol (min x mg protein)-1, i.e., when K+ depleted most of the deltaP, and at ADP concentrations below the Km, the rate of ATP synthesis was essentially the same as in the absence of K+. At saturating ADP, the rate of ATP synthesis in the presence of K+ was about 60% of the rate observed without K+. The synthesis of ATP by yeast mitochondria was inhibited by oligomycin or uncouplers. K+ had no effects on rat liver mitochondria. Adenylate kinase activity was much smaller in yeast mitochondria than in rat liver mitochondria and thus did not account for the synthesis of ATP observed in the presence of K+. The effects of K+ on the deltaP of yeast mitochondria were prevented by increasing concentrations of phosphate (1 to 4 mM). At 4 mM phosphate, the deltaP was always above 200 mV and the kinetics of ATP synthesis were as follows: 0 K+ Km = 10.0 microM and Vmax = 88.3 nmol (min x mg protein)-1. At 20 mM K+, Km = 7.4 microM and Vmax = 133 nmol (min x mg protein)-1.

Adenosine Triphosphate↗
PubMed2002

Changes of myocardial mitochondrial Ca(2+) transport and mechanism in the early stage after severe burns.

OBJECTIVE: To investigate the change of myocardial mitochondrial Ca(2+) transport and its mechanism in the early stage after burns. METHODS: Forty-eight Wistar rats were randomized into a normal control group (n=8) and a burns group (n=40). The rats of the burns group were given a 30%TBSA full-thickness. Myocardial mitochondria were isolated from normal and scalded rats which were sacrificed at the 1st, 3rd, 6th, 12th and 24th hour post-burn. Mitochondrial Ca(2+) transport velocity, membrane potential (MP), ATP content and cytosolic Ca(2+) concentration [Ca(2+)](c) were determined. The effects of exogenous ATP on mitochondrial Ca(2+) transport velocity were also investigated. RESULTS: Mitochondrial Ca(2+) uptake velocity of the 1st hour post-burn was higher than that of the control, and Ca(2+) release velocity did not change significantly, but mitochondrial Ca(2+) transport velocity, MP and ATP content were all decreased at the 3rd, 6th, 12th and 24th hour post-burn. Mitochondrial Ca(2+) uptake velocity was positively correlated with MP after burn, and Ca(2+) release velocity with mitochondrial ATP content. [Ca(2+)](c) was increased at the 3rd, 6th, 12th and 24th hour post-burn. Exogenous ATP increased myocardial mitochondrial Ca(2+) uptake velocity of rats at the 3rd and 6th hour post-burn and Ca(2+) release velocity at the 3rd, 6th and 12th hour post-burn. CONCLUSIONS: Increase of [Ca(2+)](c) led to reinforcement of mitochondrial Ca(2+) uptake at the beginning of the post-burns period. ATP depletion and MP collapse cause myocardial mitochondrial Ca(2+) transport disorder in the following stages.

Adenosine Triphosphate↗
PubMed2005

[Rigor mortis -- a definite sign of death?].

In the past years an ongoing controversial debate exists in Germany, regarding quality of the coroner's inquest and declaration of death by physicians. We report the case of a 90-year old female, who was found after an unknown time following a suicide attempt with benzodiazepine. The examination of the patient showed livores (mortis?) on the left forearm and left lower leg. Moreover, rigor (mortis?) of the left arm was apparent which prevented arm flexion and extension. The hypothermic patient with insufficient respiration was intubated and mechanically ventilated. Chest compressions were not performed, because central pulses were (hardly) palpable and a sinus bradycardia 45/min (AV-block 2 degrees and sole premature ventricular complexes) was present. After placement of an intravenous line (17 G, external jugular vein) the hemodynamic situation was stabilized with intermittent boli of epinephrine and with sodium bicarbonate. With improved circulation livores and rigor disappeared. In the present case a minimal central circulation was noted, which could be stabilized, despite the presence of certain signs of death ( livores and rigor mortis). Considering the finding of an abrogated peripheral perfusion (livores), we postulate a centripetal collapse of glycogen and ATP supply in the patients left arm (rigor), which was restored after resuscitation and reperfusion. Thus, it appears that livores and rigor are not sensitive enough to exclude a vita minima, in particular in hypothermic patients with intoxications. Consequently a careful ABC-check should be performed even in the presence of apparently certain signs of death, to avoid underdiagnosing a vita minima. Additional ECG- monitoring is required to reduce the rate of false positive declarations of death. To what extent basic life support by paramedics should commence when rigor and livores are present until physician DNR order, deserves further discussion.

Aged↗
PubMed2000

Oxidative phosphorylation supported by an alternative respiratory pathway in mitochondria from Euglena.

The effect of antimycin, myxothiazol, 2-heptyl-4-hydroxyquinoline-N-oxide, stigmatellin and cyanide on respiration, ATP synthesis, cytochrome c reductase, and membrane potential in mitochondria isolated from dark-grown Euglena cells was determined. With L-lactate as substrate, ATP synthesis was partially inhibited by antimycin, but the other four inhibitors completely abolished the process. Cyanide also inhibited the antimycin-resistant ATP synthesis. Membrane potential was collapsed (<60 mV) by cyanide and stigmatellin. However, in the presence of antimycin, a H(+)60 mV) that sufficed to drive ATP synthesis remained. Cytochrome c reductase, with L-lactate as donor, was diminished by antimycin and myxothiazol. Cytochrome bc(1) complex activity was fully inhibited by antimycin, but it was resistant to myxothiazol. Stigmatellin inhibited both L-lactate-dependent cytochrome c reductase and cytochrome bc(1) complex activities. Respiration was partially inhibited by the five inhibitors. The cyanide-resistant respiration was strongly inhibited by diphenylamine, n-propyl-gallate, salicylhydroxamic acid and disulfiram. Based on these results, a model of the respiratory chain of Euglena mitochondria is proposed, in which a quinol-cytochrome c oxidoreductase resistant to antimycin, and a quinol oxidase resistant to antimycin and cyanide are included.

Adenosine Triphosphate↗
PubMed2001

Mitochondrial K(ATP) channel activation reduces anoxic injury by restoring mitochondrial membrane potential.

Mitochondrial membrane potential (DeltaPsi(m)) is severely compromised in the myocardium after ischemia-reperfusion and triggers apoptotic events leading to cell demise. This study tests the hypothesis that mitochondrial ATP-sensitive K(+) (mitoK(ATP)) channel activation prevents the collapse of DeltaPsi(m) in myocytes during anoxia-reoxygenation (A-R) and is responsible for cell protection via inhibition of apoptosis. After 3-h anoxia and 2-h reoxygenation, the cultured myocytes underwent extensive damage, as evidenced by decreased cell viability, compromised membrane permeability, increased apoptosis, and decreased ATP concentration. Mitochondria in A-R myocytes were swollen and fuzzy as shown after staining with Mito Tracker Orange CMTMRos and in an electron microscope and exhibited a collapsed DeltaPsi(m), as monitored by 5,5',6,6'-tetrachloro-1,1',3,3'-tetraethylbenzimidazolcarbocyanine iodide (JC-1). Cytochrome c was released from mitochondria into the cytosol as demonstrated by cytochrome c immunostaining. Activation of mitoK(ATP) channel with diazoxide (100 micromol/l) resulted in a significant protection against mitochondrial damage, ATP depletion, cytochrome c loss, and stabilized DeltaPsi(m). This protection was blocked by 5-hydroxydecanoate (500 micromol/l), a mitoK(ATP) channel-selective inhibitor, but not by HMR-1098 (30 micromol/l), a putative sarcolemmal K(ATP) channel-selective inhibitor. Dissipation of DeltaPsi(m) also leads to opening of mitochondrial permeability transition pore, which was prevented by cyclosporin A. The data support the hypothesis that A-R disrupts DeltaPsi(m) and induces apoptosis, which are prevented by the activation of the mitoK(ATP) channel. This further emphasizes the therapeutic significance of mitoK(ATP) channel agonists in the prevention of ischemia-reperfusion cell injury.

Animals↗
PubMed2003

Complex II defect via down-regulation of iron-sulfur subunit induces mitochondrial dysfunction and cell cycle delay in iron chelation-induced senescence-associated growth arrest.

Mitochondria play a pivotal role as an ATP generator in aerobically growing cells, and their defects have long been implicated in the cellular aging process, although its detailed underlying mechanisms remain unclear. Recently, we found that, in the cellular senescent process of Chang cells induced by desferroxamine mesylate, an iron chelator, a significant decrease of intracellular ATP level was accompanied by decline in complex II activity, which preceded acquisition of the senescent phenotype. In the present study, we investigated the mechanism of how the mitochondrial ATP productivity was damaged by iron chelation and how complex II defect was involved in the senescent arrest. The ATP loss was irreversible and accompanied by sustained collapse of mitochondrial membrane potential (Delta psi m), but the ATP loss itself did not seem to be essential in progression to the senescent arrest. The Delta psi m disruption was due to decreased mitochondrial respiration, which was primarily associated with the defective complex II activity. Furthermore, we found that the declined activity of complex II was mainly due to down-regulation of protein expression of the iron-sulfur subunit, which was associated with the irreversibility of the arrest. Finally, we demonstrated that specific inhibition of complex II with 2-thenoyltrifluoroacetone induced overall delay of the cell cycle, suggesting that the delayed arrest by desferroxamine mesylate might be in part due to inhibition of complex II activity. Taken together, our results suggest that complex II might be considered as one of the primary factors to regulate mitochondrial respiratory function by responding to the cellular iron level, thereby influencing cellular growth.

Adenosine Triphosphate↗
PubMed1995

Characteristics of Fe(II)ATP complex-induced damage to the rat liver mitochondrial membrane.

It is well established that several iron complexes can induce oxidative damage in hepatic mitochondrial membranes by catalyzing the formation of OH radicals and/or by promoting lipid peroxidation. This is a relevant process for the molecular basis of iron overload diseases. The present work demonstrates that Fe(II)ATP complexes (5-50 microM) promote an oxygen consumption burst in a suspension of isolated rat liver mitochondria (either in the absence or presence of Antimycin A), caused mainly by lipid peroxidation. Fe(II)ATP alone induced small levels of oxygen uptake but no burst. The time course of Fe(II)ATP oxidation to Fe(II)ATP in the extramitochondrial media also reveals a simultaneous 'burst phase'. The iron chelator Desferal (DFO) or the chain-break antioxidant butylated hydroxytoluene (BHT) fully prevented both lipid peroxidation (quantified as oxygen uptake burst) and mitochondrial swelling. DFO and BHT were capable of stopping the ongoing process of peroxidation at any point of their addition to the mitochondrial suspension. Conversely, DFO and BHT only halted the Fe(II)ATP-induced mitochondrial swelling at the onset of the process. Fe(II)ATP could also cause the collapse of mitochondrial potential, which was protected by BHT if added at the onset of the damaging process. These results, as well as correlation studies between peroxidation and mitochondrial swelling, suggest that a two phase process is occurring during Fe(II)ATP-induced mitochondrial damage: one dependent and another independent of lipid peroxidation. The involvement of lipid peroxidation in the overall process of mitochondrial membrane injury is discussed.

Adenosine Triphosphate↗
PubMed1995

The mechanism for the ATP-induced uncoupling of respiration in mitochondria of the yeast Saccharomyces cerevisiae.

We have recently reported that ATP induces an uncoupling pathway in Saccharomyces cerevisiae mitochondria [Prieto, Bouillaud, Ricquier and Rial (1992) Eur. J. Biochem. 208, 487-491]. The presence of this pathway would explain the reported low efficiency of oxidative phosphorylation in S. cerevisiae, and may represent one of the postulated energy-dissipating mechanisms present in these yeasts. In this paper we demonstrate that ATP exerts its action in two steps: first, at low ATP/Pi ratios, it increases the respiratory-chain activity, probably by altering the kinetic properties of cytochrome c oxidase. Second, at higher ATP/Pi ratios, an increase in membrane permeability leads to a collapse in membrane potential. The ATP effect on cytochrome c oxidase corroborates a recent report showing that ATP interacts specifically with yeast cytochrome oxidase, stimulating its activity [Taanman and Capaldi (1993) J. Biol. Chem. 268, 18754-18761].

Adenosine Triphosphate↗
PubMed2003

Outer mitochondrial membrane permeabilization during apoptosis triggers caspase-independent mitochondrial and caspase-dependent plasma membrane potential depolarization: a single-cell analysis.

Little is known about the temporal relationship between mitochondrial and plasma membrane potential changes and outer mitochondrial membrane permeabilization during apoptosis. Confocal imaging of breast carcinoma and HeLa cells stably transfected with cytochrome-C-GFP demonstrated that mitochondria rapidly depolarized after the release of the fusion protein into the cytosol. Of note, mitochondria did not completely depolarize but established a new steady-state level that could be further dissipated by treatment with the protonophore carbonyl cyanide p-trifluoromethoxy-phenylhydrazone. Treatment with the F(O)F(1)-ATP-synthase inhibitor oligomycin likewise induced a collapse of this steady-state level, suggesting that F(O)F(1)-ATP-synthase reversal maintained mitochondrial potential after outer mitochondrial membrane permeabilization. Treatment with a broad spectrum caspase inhibitor failed to inhibit the partial depolarization of mitochondria during apoptosis, yet potently abolished the activation of effector caspases detected by fluorescence resonance energy transfer analysis in the same experiment. Interestingly, the onset of mitochondrial depolarization was always coupled with a depolarization of the plasma membrane potential. This was associated with the degradation of the regulatory Na(+)/K(+)-ATPase beta-subunit, and both events were blocked by caspase inhibition. Our results demonstrate that outer mitochondrial membrane permeabilization coordinates the depolarization of both membrane potentials during apoptosis.

Apoptosis↗
PubMed1996

Mitochondrial bioenergetics as affected by cationic detergents.

This paper examines the accumulation and toxicity mechanism of a cationic detergent, cetyltrimethylammonium (bromide) (CTAB), in energized rat liver mitochondria. The results suggest that: (1) the CTAB ion is accumulated in the mitochondrial matrix by a membrane potential-driven uptake mechanism; (2) accumulation may lead to a toxic effect, since it gives rise to collapse of the mitochondrial membrane potential (delta phi) which is correlated with ATP synthesis and which regulates Ca++ uptake; (3) collapse of delta phi may be due to enhanced permeability of the mitochondrial membrane to the ions (detergent effect); and (4) delta phi collapse and Ca++ and K+ release were also observed in another cationic detergent, NTAB, but not in the presence of anionic detergents.

Adenosine Triphosphate↗
PubMed1980

Role of the proton electrochemical gradient in monoamine transport by bovine chromaffin granules.

The role of the transmembrane potential (delta phi), the proton concentration gradient (delta pH) and the proton electrochemical gradient (delta gamma H+) in monoamine uptake by bovine chromaffin granules or ghosts was investigated. In presence of ATP the permeant anion SCN- collapsed the delta phi (inside positive) and inhibited monoamine uptake by granules or well buffered ghosts. With lightly buffered ghosts, SCN- induced an acidification which resulted in a low inhibition of uptake. Cation efflux as well as anion influx affected the delta phi, and a transient valinomycin-mediated K+ efflux induced a lag in the uptake. The delta pH-driven noradrenalin uptake was also sensitive to delta phi, since superimposing a positive or a negative delta phi to the delta pH, respectively, increased or decreased the rate of noradrenalin accumulation. A delta pH was required for this increase of uptake rate, adrenalin accumulation. A delta pH was required for this increase of uptake rate, which was proportional to the delta phi. The pH-dependence of the ATP-induced monoamine uptake by granules pointed to the delta gamma H+ as the driving force. In contrast with the rate of uptake, which was not dependent on the anions present, the extent of amine incorporation was decreased when the internal anionic buffer concentration was decreased and, at a low internal buffer concentration, when ATP anion transport was blocked.

Adenosine Triphosphate↗
PubMed1999

Apoptosis and growth inhibition in malignant lymphocytes after treatment with arsenic trioxide at clinically achievable concentrations.

BACKGROUND: Arsenic trioxide (As2O3) can induce clinical remission in patients with acute promyelocytic leukemia via induction of differentiation and programmed cell death (apoptosis). We investigated the effects of As2O3 on a panel of malignant lymphocytes to determine whether growth-inhibitory and apoptotic effects of As2O3 can be observed in these cells at clinically achievable concentrations. METHODS: Eight malignant lymphocytic cell lines and primary cultures of lymphocytic leukemia and lymphoma cells were treated with As2O3, with or without dithiothreitol (DTT) or buthionine sulfoximine (BSO) (an inhibitor of glutathione synthesis). Apoptosis was assessed by cell morphology, flow cytometry, annexin V protein level, and terminal deoxynucleotidyl transferase labeling of DNA fragments. Cellular proliferation was determined by 5-bromo-2'-deoxyuridine incorporation into DNA and flow cytometry and by use of a mitotic arrest assay. Mitochondrial transmembrane potential (delta psi(m)) was measured by means of rhodamine 123 staining and flow cytometry. Protein expression was assessed by western blot analysis or immunofluorescence. RESULTS: Therapeutic concentrations of As2O3 (1-2 microM) had dual effects on malignant lymphocytes: 1) inhibition of growth through adenosine triphosphate (ATP) depletion and prolongation of cell cycle time and 2) induction of apoptosis. As2O3-induced apoptosis was preceded by delta psi(m) collapse. DTT antagonized and BSO enhanced As2O3-induced ATP depletion, delta psi(m) collapse, and apoptosis. Caspase-3 activation, usually resulting from delta psi(m) collapse, was not always associated with As2O3-induced apoptosis. As2O3 induced PML (promyelocytic leukemia) protein degradation but did not modulate expression of cell cycle-related proteins, including c-myc, retinoblastoma protein, cyclin-dependent kinase 4, cyclin D1, and p53, or expression of differentiation-related antigens. CONCLUSIONS: Substantial growth inhibition and apoptosis without evidence of differentiation were induced in most malignant lymphocytic cells treated with 1-2 microM As2O3. As2O3 may prove useful in the treatment of malignant lymphoproliferative disorders.

Adenosine Triphosphate↗
PubMed2001

Mitochondrial electron transport inhibitors cause lipid peroxidation-dependent and -independent cell death: protective role of antioxidants.

Mitochondrial electron transport inhibitors induced two distinct pathways for acute cell death: lipid peroxidation-dependent and -independent in isolated rat hepatocytes. The toxic effects of mitochondrial complex I and II inhibitors, rotenone (ROT) and thenoyltrifluoroacetone (TTFA), respectively, were dependent on oxidative stress and lipid peroxidation, while cell death induced by inhibitors of complexes III and IV, antimycin A (AA) and cyanide (CN), respectively, was caused by MMP collapse and loss of cellular ATP. Accordingly, cellular and mitochondrial antioxidant depletion or supplementation, in general, resulted in a dramatic potentiation or prevention, respectively, of toxic injury induced by complex I and II inhibitors, with little or no effect on complex III and IV inhibitor-induced toxicity. ROT-induced oxidative stress was prevented by the addition of d-alpha-tocopheryl succinate (TS) but surprisingly TS did not afford hepatocytes protection against TTFA-induced oxidative damage. TS treatment prevented ROT-induced mitochondrial lipid hydroperoxide formation but had no effect on the loss of mitochondrial GSH or cellular ATP, suggesting a mitochondrial lipid peroxidation-mediated mechanism for ROT-induced acute cell death. In contrast, only fructose treatment provided excellent cytoprotection against AA- and CN-induced toxicity. Our findings indicate that complex III and IV inhibitors cause a rapid and severe depletion of cellular ATP content resulting in acute cell death that is dependent on cellular energy impairment but not lipid peroxidation. In contrast, inhibitors of mitochondrial complex I or II moderately deplete cellular ATP levels and thus cause acute cell death via a lipid peroxidation pathway.

Adenosine Triphosphate↗
PubMed2001

Tissue oxygen tension and brain sensitivity to hypoxia.

Mammalian brain is a highly oxidative organ and although it constitutes only a small fraction of total body weight it accounts for a disproportionately large percentage of bodily oxygen consumption (in humans about 2 and 20%, respectively). Yet, the partial pressure and concentration of oxygen in the brain are low and non-uniform. There is a large number of enzymes that use O(2) as a substrate, the most important of which is cytochrome c oxidase, the key to mitochondrial ATP production. The affinity of cytochrome c oxidase for oxygen is very high, which under normal conditions ensures undiminished activity of oxidative phosphorylation down to very low P(O(2)). By contrast, many other relevant enzymes have K(m) values for oxygen within, or above, the ambient cerebral gas tension, thus making their operations very dependent on oxygen level in the physiological range. Among its multiple, versatile functions, oxygen partial pressure and concentration control production of reactive oxygen species, expression of genes and functions of ion channels. Limitation of oxygen supply to the brain below a 'critical' level reduces, and eventually blocks oxidative phosphorylation, drastically decreases cellular (ATP) and leads to a collapse of ion gradients. Neuronal activity ceases and if oxygen is not re-introduced quickly, cells die. The object of this review is to discuss briefly the central oxygen-dependent processes in mammalian brain and the short-term consequences of O(2) deprivation, but not the mechanisms of long-term adaptation to chronic hypoxia. Particular emphasis is placed on issues which have been the focus of recent attention and/or controversy.

Animals↗
PubMed1988

Thyrotropin induces the acidification of the secretory granules of parafollicular cells by increasing the chloride conductance of the granular membrane.

Secretory granules of sheep thyroid parafollicular cells contain serotonin, a serotonin-binding protein, and calcitonin. Parafollicular cells, isolated by affinity chromatography, were found to secrete serotonin when activated by thyrotropin (TSH) or elevated [Ca2+]e. TSH also induced a rise in [Ca2+]i. We studied the effect of these secretogogues on the pH difference (delta pH) across the membranes of the secretory granules of isolated parafollicular cells. The trapping of the weak bases, acridine orange or 3-(2,4 dinitro anilino)-3'-amino-N-methyl dipropylamine (DAMP), within the granules was used to evaluate delta pH. In contrast to lysosomes, which served as an internal control, the secretory granules of resting parafollicular cells displayed a limited and variable ability to trap either acridine orange or 3-(2,4 dinitro anilino)-3'-amino-N-methyl dipropylamine; however, when parafollicular cells were stimulated with TSH or elevated [Ca2+]e, the granules acidified. Weak base trapping was also used to evaluate the ATP-driven H+ translocation into isolated parafollicular granules. The isolated parafollicular granules did not acidify in response to addition of ATP unless their transmembrane potential was collapsed by the K+ ionophore, valinomycin. Secretory granules isolated from TSH-treated parafollicular cells had a high chloride conductance than did granules isolated similarly from untreated cells. Furthermore, ATP-driven H+ translocation into parafollicular granules isolated from TSH-stimulated parafollicular cells occurred even in the absence of valinomycin. These results demonstrate that secretogogues can regulate the internal pH of the serotonin-storing secretory granules of parafollicular cells by opening a chloride channel associated with the granule membrane. This is the first demonstration that the pH of secretory vesicles may be modified by altering the conductance of a counterion for the H+ translocating ATPase.

Adenosine Triphosphate↗
PubMed1998

Lacticin 3147, a broad-spectrum bacteriocin which selectively dissipates the membrane potential.

Lacticin 3147 is a broad-spectrum bacteriocin produced by Lactococcus lactis subsp. lactis DPC3147 (M. P. Ryan, M. C. Rea, C. Hill, and R. P. Ross, Appl. Environ. Microbiol. 62:612-619, 1996). Partial purification of the bacteriocin by hydrophobic interaction chromatography and reverse-phase fast protein liquid chromatography revealed that two components are required for full activity. Lacticin 3147 is bactericidal against L. lactis, Listeria monocytogenes, and Bacillus subtilis; at low concentrations of the bacteriocin, bactericidal activity is enhanced when target cells are energized. This finding suggests that the presence of a proton motive force promotes the interaction of the bacteriocin with the cytoplasmic membrane, leading to the formation of pores at these low lacticin 3147 concentrations. These pores were shown to be selective for K+ ions and inorganic phosphate. The loss of these ions resulted in immediate dissipation of the membrane potential and hydrolysis of internal ATP, leading to an eventual collapse of the pH gradient at the membrane and ultimately to cell death. Our results suggest that lacticin 3147 is a pore-forming bacteriocin which acts on a broad range of gram-positive bacteria.

Adenosine Triphosphate↗