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Results for “mitochondria dynamics”

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At least 127 records · Page 7Linked to original sources
PubMed1999

Mitochondria regulate the Ca(2+)-exocytosis relationship of bovine adrenal chromaffin cells.

The present study expands the contemporary view of mitochondria as important participants in cellular Ca(2+) dynamics and provides evidence that mitochondria regulate the supply of release-competent secretory granules. Using pharmacological probes to inhibit mitochondrial Ca(2+) import, the ability of mitochondria to modulate secretory activity in single, patch-clamped bovine chromaffin cells was examined by simultaneously monitoring rapid changes in membrane surface area (DeltaC(m)) and cytosolic Ca(2+) levels ([Ca(2+)](c)). Repetitive step depolarizations or action potential waveforms were found to raise the [Ca(2+)](c) of chromaffin cells into the 1 microM to tens of micromolar range. Inhibiting mitochondria by treatment with carbonyl cyanide p-(trifuoro-methoxy)phenylhydrazone, antimycin-oligomycin, or ruthenium red revealed that mitochondria are a prominent component for the clearance of Ca(2+) that entered via voltage-activated Ca(2+) channels. Disruption of cellular Ca(2+) homeostasis by poisoning mitochondria enhanced the secretory responsiveness of chromaffin cells by increasing the amplitude of the transient rise and the time course of recovery to baseline of the evoked Delta[Ca(2+)](c). The enhancement of the secretory response was represented by significant deviation of the Ca(2+)-exocytosis relationship from a standard relationship that equates Ca(2+) influx and DeltaC(m). Thus, mitochondria would play a critical role in the control of secretory activity in chromaffin cells that undergo tonic or repetitive depolarizing activity, likely by limiting the Ca(2+)-dependent activation of specific proteins that recruit or prime secretory granules for exocytosis.

Action Potentials↗
PubMed1990

Dynamic microstructure and hydration of peroxidized membrane of rat cardiac mitochondria and effects of adriamycin.

Nanosecond time-resolved fluorometry of diphenyl hexatriene, DPH, fluorescence was used to study the effects of lipid peroxidation caused by NADH or adriamycin treatment on the dynamic microstructure of mitochondrial membranes from rat myocardium. Isolated mitochondria were incubated with NADH, FeCl3, and ADP, or with adriamycin. Parameters for microdynamics were calculated from the fluorescence intensity and anisotropy decay curves for DPH fluorescence. Peroxidized lipids were measured as malondialdehyde (MDA) resulting from the thiobarbiturate reaction. As peroxidized lipids accumulated, the membrane viscosity increased and the wobbling angle of the phospholipids decreased. The structural changes induced in unsaturated phospholipids by peroxidation probably increased the friction of neighboring phospholipids and restricted the range of their wobbling motion. The fluorescence intensity and fluorescence lifetimes decreased significantly when MDA was higher than 10 nmol/mg protein. These alterations in the behavior of DPH fluorescence strongly suggest that the hydration of the phospholipid layer of the mitochondria is occurring as a consequence of lipid peroxidation, since the fluorophore, DPH, is hydrophobic and its fluorescence is known to be quenched by increasing the dielectric constant of the surrounding media. The present results provide experimental supports to the hypothesis of membrane hydration induced by lipid peroxidation.

Animals↗
PubMed2006

Abnormal Ca2+ dynamics in transgenic mice with neuron-specific mitochondrial DNA defects.

Maintenance of mitochondrial DNA (mtDNA) depends on nuclear-encoded proteins such as mtDNA polymerase (POLG), whose mutations are involved in the diseases caused by mtDNA defects including mutation and deletion. The defects in mtDNA and in intracellular Ca2+ ([Ca2+]i) homeostasis have been reported in bipolar disorder (BD). To understand the relevance of the mtDNA defects to BD, we studied transgenic (Tg) mice in which mutant POLG (mutPOLG) was expressed specifically in neurons. mtDNA defects were accumulated in the brains of mutPOLG Tg mice in an age-dependent manner and the mutant mice showed BD-like behavior. However, the molecular and cellular basis for the abnormalities has not been clarified. In this study, we investigated Ca2+ regulation by isolated mitochondria and [Ca2+]i dynamics in the neurons of mutPOLG Tg mice. Mitochondria from the mutant mice sequestered Ca2+ more rapidly, whereas Ca2+ retention capacity and membrane potential, a driving force of Ca2+ uptake, of mitochondria were unaffected. To elucidate the molecular mechanism of the altered Ca2+ uptake, we performed DNA microarray analysis and found that the expression of cyclophilin D (CyP-D), a component of the permeability transition pore, was downregulated in the brains of mutPOLG Tg mice. Cyclosporin A, an inhibitor of CyP-D, mimicked the enhanced Ca2+ uptake in mutant mice. Furthermore, G-protein-coupled receptor-mediated [Ca2+]i increase was attenuated in hippocampal neurons of the mutant mice. These findings suggest that mtDNA defects lead to enhancement of Ca2+ uptake rate via CyP-D downregulation and alter [Ca2+]i dynamics, which may be involved in the pathogenesis of BD.

Age Factors↗
PubMed1987

Organelle dynamics in lobster axons: anterograde, retrograde and stationary mitochondria.

Mitochondria in isolated motor axons from the walking legs of lobster were observed with differential interference contrast optics and video microscopic techniques. Movements of the mitochondria were analyzed in time-lapse videotape records. The mean velocity of transport in the retrograde direction (1.33 +/- 0.64 micron/s) was greater than the mean velocity of transport in the anterograde direction (0.72 +/- 0.26 micron/s). The mean lengths of the mitochondria moving in the retrograde and anterograde directions were only slightly different (6.9 microns and 5.5 microns, respectively). No correlation was found between mitochondrial length and average velocity or reciprocal velocity. The instantaneous velocities of mitochondria were distributed over a range of approximately 3 micron/s; both the anterograde and retrograde distributions contained a small proportion of values whose sign was opposite to the modal value. The variation in instantaneous velocity took place at frequencies close to 0.1 Hz. Some mitochondria displayed longitudinally oriented oscillatory movements of a similar low frequency. While the movement of most mitochondria was parallel to the axis of the axon, transverse deviations and complex circular paths were sometimes observed. Some mitochondria reversed their orientation and continued in the same direction, so that the end which had been the leading end became the trailing end. Many mitochondria immediately beneath the plasma membrane were stationary and adhered strongly to the plasma membrane when the axoplasmic structure was disrupted. In electron micrographs, fine strands connected peripheral mitochondria and the plasma membrane. These strands may anchor the stationary mitochondria to the plasma membrane.

Animals↗
PubMed2001

Dynamics of structural and functional changes in hepatocyte mitochondria of senescence-accelerated OXYS rats.

Electron microscopy showed signs of degenerative dystrophic changes in hepatocytes and structural decompensation of mitochondria in senescence-accelerated OXYS rats in comparison with Wistar rats. These signs were detected in the presence of liver mitochondria dysfunction in OXYS rats: reduced oxygen consumption rate in all metabolic states, respiratory control volume, ADP/O ratio. transmembrane potential, and phosphorylation rate. The revealed disorders in mitochondrial structure and function are the key factors in the pathogenesis of accelerated aging in OXYS rats and visceropathies characteristic of these animals.

Adenosine Triphosphate↗
PubMed2001

Mitochondrial modulation of intracellular Ca(2+) signaling.

IP3-mediated Ca(2+) release plays a fundamental role in many cell signaling processes and has been the subject of numerous modeling studies. Only recently has the important role that mitochondria play in the dynamics of intracellular Ca(2+) signaling begun to be considered in experimental work and in computational models. Mitochondria sequester large amounts of Ca(2+) and thus have a modulatory effect on intracellular Ca(2+) signaling, and mitochondrial uptake of Ca(2+), in turn, has a regulatory effect on mitochondrial function. Here we integrate a well-established model of IP3-mediated Ca(2+) signaling with a detailed model of mitochondrial Ca(2+) handling and metabolic function. The incorporation of mitochondria results in oscillations in a bistable formulation of the IP3 model, and increasing metabolic substrate decreases the frequency of these oscillations consistent with the literature. Ca(2+) spikes from the cytosol are communicated into mitochondria and are shown to induce realistic metabolic changes. The model has been formulated using a modular approach that is easy to modify and should serve as a useful basis for the investigation of questions regarding the interaction of these two systems.

Calcium↗
PubMedDate not supplied

Synaptic mitochondria and ageing: computer-assisted morphometry in rat cerebellar glomeruli.

The ultrastructural features of synaptic mitochondria have been investigated by means of computer-assisted morphometry in the cerebellar glomeruli of young, adult and old rats. The volume fraction occupied by mitochondria (volume density: Vv), the number of organelles/ microm(3) (numerical density: Nv), the average volume (V) and the average length (Sk) of the mitochondria were the parameters measured in electron microscopic photos taken at an enlargement of x 8000. Vv showed a lifespan constancy. Nv was increased in the adult group vs. the young, but it was decreased in old animals as compared with the other 2 groups of age studied. V and Sk showed the same age-dependent changes: a significant decrease in the adults and a significant increase in the old rats vs. the other groups analysed, respectively. We interpret these findings to represent age-dependent morphofunctional adaptations occurring at synaptic mitochondria as a response to actual energy demands from the synaptic connectivity they subserve. Although impaired, the dynamic morphology of synaptic mitochondria appears to be capable of consistent compensative ultrastructural rearrangements in the central nervous system of old individuals.

Journal Article↗
PubMed1996

Theoretical studies on the control of oxidative phosphorylation in muscle mitochondria: application to mitochondrial deficiencies.

1. The dynamic model of oxidative phosphorylation developed previously for rat liver mitochondria incubated with succinate was adapted for muscle mitochondria respiring on pyruvate. We introduced the following changes considering: (1) a higher external ATP/ADP ratio and an ATP/ADP carrier less displaced from equilibrium; (2) a substrate dehydrogenation more sensitive to the NADH/NAD+ ratio; and (3) the respiratory chain, ATP synthase and phosphate carrier being more displaced from equilibrium. The experimental flux control coefficients already determined in state 3 for respiratory rate and ATP synthesis were used to adjust some parameters. This new oxidative phosphorylation model enabled us to simulate the whole titration curves obtained experimentally in state 3. These curves, which mimic the effect of mitochondrial complex deficiencies on oxidative phosphorylation, show a threshold effect, which is reproduced by the model. 2. the model was also used to simulate other physiological conditions such as (i) state 3.5, conditions in-between state 4 and state 3; and (ii) hypoxic conditions. In both cases a profound change in the pattern of the control coefficients was shown. 3. This model was thus found useful in investigating a variety of new conditions, the most interesting of which can then be experimentally studied.

Adenosine Diphosphate↗
PubMed2002

Chronic administration of EGb 761 modulates synaptic and mitochondrial plasticity in adult vitamin E-deficient rats.

A computer-assisted morphometric study has been carried out on synaptic junctions and synaptic mitochondria in the dentate gyrus supragranular layer of vitamin E-deficient rats undergone chronic administration of the extract EGb 761 from Ginkgo biloba leaves (100 mg/kg body weight, daily, from 4 to 7 months of age). Control animals were fed with the vitamin E-deficient diet from 1 to 7 months of age. Numeric density (Nv), surface density (Sv) and average size of the synaptic junctions (S), mitochondrial numeric density (Nvm), volume density (Vv) and average volume (V) were the measured parameters. In EGb 761-treated animals, Nv was significantly increased and S significantly decreased, while Sv was unchanged. EGb 761 administration resulted in an increased percentage of synapses of smaller size. In EGb 761-treated rats, Nvm significantly increased and V significantly decreased, while no significant difference of Vv was found. The population of synaptic mitochondria in EGb 761 -treated animals was composed of a higher number of smaller organelles. The measured parameters report on the structural dynamics of synapses and mitochondria, thus our findings support that EGb 761 administration is able to improve the physiological adaptive capacities of the investigated structures by a positive modulation of their morphofunctional features.

Animals↗
PubMed2005

Calcium-dependent dephosphorylation of brain mitochondrial calcium/cAMP response element binding protein (CREB).

Calcium-mediated signaling regulates nuclear gene transcription by calcium/cAMP response element binding protein (CREB) via calcium-dependent kinases and phosphatases. This study tested the hypothesis that CREB is also present in mitochondria and subject to dynamic calcium-dependent modulation of its phosphorylation state. Antibodies to CREB and phosphorylated CREB (pCREB) were used to demonstrate the presence of both forms in isolated mitochondria and mitoplasts from rat brain. When energized mitochondria were exposed to increasing concentrations of Ca2+ in the physiological range, pCREB was lost while total CREB remained constant. In the presence of Ru360, an inhibitor of the mitochondrial Ca2+ uptake uniporter, calcium-dependent loss of pCREB levels was attenuated, suggesting that intramitochondrial calcium plays an important role in pCREB dephosphorylation. pCREB dephosphorylation was not, however, inhibited by the phosphatase inhibitors okadaic acid and Tacrolimus. In the absence of Ca2+, CREB phosphorylation was elevated by the addition of ATP to the mitochondrial suspension. Exposure of mitochondria to the pore-forming molecule alamethicin that causes osmotic swelling and release of intermembrane proteins enriched mitochondrial pCREB immunoreactivity. These results further suggest that mitochondrial CREB is located in the matrix or inner membrane and that a kinase and a calcium-dependent phosphatase regulate its phosphorylation state.

Adenosine Triphosphate↗
PubMed1996

Theoretical studies on control of oxidative phosphorylation in muscle mitochondria at different energy demands and oxygen concentrations.

The mathematical dynamic model of oxidative phosphorylation in muscle mitochondria developed previously was used to calculate the flux control coefficients of particular steps of this process in isolated mitochondria at different amounts of hexokinase and oxygen concentrations. The pattern of control was completely different under different conditions. For normoxic concentration, the main controlling steps in state 4, state 3.5 and state 3 were proton leak, ATP usage (hexokinase) and complex III, respectively. The pattern of control in state 4 was not changed at hypoxic oxygen concentration, while in state 3.5 and state 3 much of the control was shifted from other steps to cytochrome oxidase. The implications of the theoretical results obtained for the regulation of oxidative phosphorylation in intact muscle are discussed.

Adenosine Triphosphate↗
PubMed1989

Detection of mitochondrial membrane damages in myocardial ischemia with ESR spin labeling technique.

The ultrastructure and membrane fluidity were examined in two fractions of myocardial mitochondria isolated from the ischemic region following occlusion of the circumflex coronary artery of the dog. Transmission electron microscopy revealed that 60 min of ischemia produced more structural change in the subsarcolemmal mitochondria than in the intermyofibrillar mitochondria. Changes in the dynamic properties of the mitochondrial membranes were examined using the spin labeling technique with electron spin resonance (ESR). From the ESR spectra, the membrane fluidity of the subsarcolemmal mitochondria was found to decrease significantly after ischemic injury, whereas no difference was observed in intermyofibrillar mitochondria. In addition, a negative correlation between the increase of order parameter S and dysfunction of respiratory responses of subsarcolemmal mitochondria was found. These results suggest that the two fractions of mitochondria in the myocardium showed different responses to acute ischemic injury. The damage to mitochondrial membranes occurred during the period of ischemia.

Animals↗
PubMed2000

The Golgi apparatus segregates from the lysosomal/acrosomal vesicle during rhesus spermiogenesis: structural alterations.

The acrosome is an acidic secretory vesicle containing hydrolytic enzymes that are involved in the sperm's passage across the zona pellucida. Imaging of the acrosomal vesicle and the Golgi apparatus in live rhesus monkey spermatids was accomplished by using the vital fluorescent probe LysoTracker DND-26. Concurrently, the dynamics of living spermatid mitochondria was visualized using the specific probe MitoTracker CMTRos and LysoTracker DND-26 detected the acrosomal vesicle from its formation through spermatid differentiation. LysoTracker DND-26 also labeled the Golgi apparatus in spermatogenic cells. In spermatocytes the Golgi is spherical and, in round spermatids, it is localized over the acrosomal vesicle, as confirmed by using polyclonal antibodies against Golgin-95/GM130, Golgin-97, and Golgin-160. Using both live LysoTracker DND-26 imaging and Golgi antibodies, we found that the Golgi apparatus is cast off from the acrosomal vesicle and migrates toward the sperm tail in elongated spermatids. The Golgi is discarded in the cytoplasmic droplet and is undetectable in mature ejaculated spermatozoa. The combined utilization of three vital fluorescent probes (Hoechst 33342, LysoTracker DND-26, and MitoTracker CMTRos) permits the dynamic imaging of four organelles during primate spermiogenesis: the nucleus, the mitochondria, the acrosomal vesicle, and the Golgi apparatus.

Acrosin↗
PubMed2003

Mechanisms of mitochondria-neurofilament interactions.

Mitochondria are localized to regions of the cell where ATP consumption is high and are dispersed according to changes in local energy needs. In addition to motion directed by molecular motors, mitochondrial distribution in neuronal cells appears to depend on the docking of mitochondria to microtubules and neurofilaments. We examined interactions between mitochondria and neurofilaments using fluorescence microscopy, dynamic light scattering, atomic force microscopy, and sedimentation assays. Mitochondria-neurofilament interactions depend on mitochondrial membrane potential, as revealed by staining with a membrane potential sensitive dye (JC-1) in the presence of substrates/ADP or uncouplers (valinomycin/carbonyl cyanide p-(trifluoromethoxy)phenylhydrazone) and are affected by the phosphorylation status of neurofilaments and neurofilament sidearms. Antibodies against the neurofilament heavy subunit disrupt binding between mitochondria and neurofilaments, and isolated neurofilament sidearms alone interact with mitochondria, suggesting that they mediate the interactions between the two structures. These data suggest that specific and regulated mitochondrial-neurofilament interactions occur in situ and may contribute to the dynamic distribution of these organelles within the cytoplasm of neurons.

Animals↗
PubMed1986

Entry and exit pathways of CO2 in rat liver mitochondria respiring in a bicarbonate buffer system.

The dynamics and pathways of CO2 movements across the membranes of mitochondria respiring in vitro in a CO2/HCO-3 buffer at concentrations close to that in intact rat tissues were continuously monitored with a gas-permeable CO2-sensitive electrode. O2 uptake and pH changes were monitored simultaneously. Factors affecting CO2 entry were examined under conditions in which CO2 uptake was coupled to electrophoretic influx of K+ (in the presence of valinomycin) or Ca2+. The role of mitochondrial carbonic anhydrase (EC 4.2.1.1) in CO2 entry was evaluated by comparison of CO2 uptake by rat liver mitochondria, which possess carbonic anhydrase, versus rat heart mitochondria, which lack carbonic anhydrase. Such studies showed that matrix carbonic anhydrase activity is essential for rapid net uptake of CO2 with K+ or Ca2+. Studies with acetazolamide (Diamox), a potent inhibitor of carbonic anhydrase, confirmed the requirement of matrix carbonic anhydrase for net CO2 uptake. It was shown that at pH 7.2 the major species leaving respiring mitochondria is dissolved CO2, rather than HCO-3 or H2CO3 suggested by earlier reports. Efflux of endogenous CO2/HCO-3 is significantly inhibited by inhibitors of the dicarboxylate and tricarboxylate transport systems of the rat liver inner membrane. The possibility that these anion carriers mediate outward transport of HCO-3 is discussed.

Acetazolamide↗
PubMed2006

Sustained activity of calcium release-activated calcium channels requires translocation of mitochondria to the plasma membrane.

A rise of the intracellular Ca(2+) concentration has multiple signaling functions. Sustained Ca(2+) influx across plasma membrane through calcium release-activated calcium (CRAC) channels is required for T-cell development in the thymus, gene transcription, and proliferation and differentiation of naïve T-cells into armed effectors cells. Intracellular Ca(2+) signals are shaped by mitochondria, which function as a highly dynamic Ca(2+) buffer. However, the precise role of mitochondria for Ca(2+)-dependent T-cell activation is unknown. Here we have shown that mitochondria are translocated to the plasma membrane as a consequence of Ca(2+) influx and that this directed movement is essential to sustain Ca(2+) influx through CRAC channels. The decreased distance between mitochondria and the plasma membrane enabled mitochondria to take up large amounts of inflowing Ca(2+) at the plasma membrane, thereby preventing Ca(2+)-dependent inactivation of CRAC channels and sustaining Ca(2+) signals. Inhibition of kinesin-dependent mitochondrial movement along microtubules abolished mitochondrial translocation and reduced sustained Ca(2+) signals. Our results show how a directed movement of mitochondria is used to control important cellular functions such as Ca(2+)-dependent T-cell activation.

Biological Transport, Active↗