Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “mitochondria dynamics”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 163 records · Page 9Linked to original sources
PubMed2006

Maintenance of the metabolic homeostasis of the heart: developing a systems analysis approach.

The heart is almost unique in the body with a constant requirement to conduct work well beyond the normal maintenance of cellular integrity. With this constant workload, it is not surprising that cardiac energy conversion is highly specialized to maintain a constant supply of energy. This maintenance of cellular metabolites during alterations in workload has been termed metabolic homeostasis. Here we discuss our efforts to understand the cellular and mitochondrial control network that orchestrates the metabolic homeostasis of the heart. This begins with a better definition of the metabolic pathways, acute posttranslational control sites, and proper kinetic evaluation of the reaction steps in the intact mitochondrial environment. First, a quantitative model of mitochondrial energy conversion is presented and demonstrates several serious gaps in our knowledge of this process. Toward filling these gaps, screens of the entire mitochondrial proteome have been conducted to establish the metabolic pathways that need to be considered. In addition, the dynamic phosphoproteome of intact mitochondria, using 2D gel electrophoresis coupled to (32)P labeling, has revealed a remarkably extensive protein phosphorylation network throughout the mitochondrial metabolic network that has essentially been overlooked. Initial studies on evaluating the functional significance of these protein phosphorylations and the kinase-phosphatase system involved will be reviewed. One of the major deficits in the consensus quantitative model of oxidative phosphorylation to explain intact mitochondria activities is in complex I, where even the initiation of Nicotinamide Adenine Dinucleotide (reduced) (NADH) oxidation is problematical using in vitro kinetic data. Studies will be described where the NADH binding and oxidation kinetics at complex I in the intact mitochondria were determined using fluorescence lifetime and enzyme dependent-fluorescence recovery after photo-oxidation (ED-FRAP) techniques. These later studies suggest that matrix NADH binding characteristics are much different (>10(3) binding constant errors) than isolated proteins. In addition, complex I is far from equilibrium and may play an important role in regulating the rate of reducing equivalent delivery to the cytochromes.

Animals↗
PubMedDate not supplied

[The effect of GABA-ergic agents on oxidative phosphorylation in the brain mitochondria in traumatic edema].

The condition of oxidative phosphorylation in the rat brain mitochondria was studied polarographically in dynamics of the brain traumatic edema. It was found that 24 hours after the trauma the rate of oxidation in mitochondria decreased and the degree of conjugation in the respiratory chain compensatorily increased. Piracetam (1 g/kg), phenibut (50 mg/kg) and to a lesser degree sodium oxybutyrate (0.2 g/kg) prevented the 'changes and enhanced the compensatory capacities of mitochondria during the development of traumatic edema of the brain.

Animals↗
PubMed2005

The WD40 protein Caf4p is a component of the mitochondrial fission machinery and recruits Dnm1p to mitochondria.

The mitochondrial division machinery regulates mitochondrial dynamics and consists of Fis1p, Mdv1p, and Dnm1p. Mitochondrial division relies on the recruitment of the dynamin-related protein Dnm1p to mitochondria. Dnm1p recruitment depends on the mitochondrial outer membrane protein Fis1p. Mdv1p interacts with Fis1p and Dnm1p, but is thought to act at a late step during fission because Mdv1p is dispensable for Dnm1p localization. We identify the WD40 repeat protein Caf4p as a Fis1p-associated protein that localizes to mitochondria in a Fis1p-dependent manner. Caf4p interacts with each component of the fission apparatus: with Fis1p and Mdv1p through its NH2-terminal half and with Dnm1p through its COOH-terminal WD40 domain. We demonstrate that mdv1delta yeast contain residual mitochondrial fission due to the redundant activity of Caf4p. Moreover, recruitment of Dnm1p to mitochondria is disrupted in mdv1delta caf4delta yeast, demonstrating that Mdv1p and Caf4p are molecular adaptors that recruit Dnm1p to mitochondrial fission sites. Our studies support a revised model for assembly of the mitochondrial fission apparatus.

Adaptor Proteins, Signal Transducing↗
PubMed2004

Endophilin B1 is required for the maintenance of mitochondrial morphology.

We report that a fatty acyl transferase, endophilin B1, is required for maintenance of mitochondrial morphology. Down-regulation of this protein or overexpression of endophilin B1 lacking the NH(2)-terminal lipid-modifying domain causes striking alterations of the mitochondrial distribution and morphology. Dissociation of the outer mitochondrial membrane compartment from that of the matrix, and formation of vesicles and tubules of outer mitochondrial membrane, was also observed in both endophilin B1 knockdown cells and after overexpression of the truncated protein, indicating that endophilin B1 is required for the regulation of the outer mitochondrial membrane dynamics. We also show that endophilin B1 translocates to the mitochondria during the synchronous remodeling of the mitochondrial network that has been described to occur during apoptosis. Double knockdown of endophilin B1 and Drp1 leads to a mitochondrial phenotype identical to that of the Drp1 single knockdown, a result consistent with Drp1 acting upstream of endophilin B1 in the maintenance of morphological dynamics of mitochondria.

Acyltransferases↗
PubMed2000

Respiring mitochondria determine the pattern of activation and inactivation of the store-operated Ca(2+) current I(CRAC).

In eukaryotic cells, hormones and neurotransmitters that engage the phosphoinositide pathway evoke a biphasic increase in intracellular free Ca(2+) concentration: an initial transient release of Ca(2+) from intracellular stores is followed by a sustained phase of Ca(2+) influx. This influx is generally store dependent. Most attention has focused on the link between the endoplasmic reticulum and store-operated Ca(2+) channels in the plasma membrane. Here, we describe that respiring mitochondria are also essential for the activation of macroscopic store-operated Ca(2+) currents under physiological conditions of weak intracellular Ca(2+) buffering. We further show that Ca(2+)-dependent slow inactivation of Ca(2+) influx, a widespread but poorly understood phenomenon, is regulated by mitochondrial buffering of cytosolic Ca(2+). Thus, by enabling macroscopic store-operated Ca(2+) current to activate, and then by controlling its extent and duration, mitochondria play a crucial role in all stages of store-operated Ca(2+) influx. Store-operated Ca(2+) entry reflects a dynamic interplay between endoplasmic reticulum, mitochondria and plasma membrane.

Animals↗
PubMedDate not supplied

Disturbance of myocardial energy liberation in experimental charcoal embolism of canine pulmonary artery.

Experimental charcoal embolism of the pulmonary artery was produced in dogs. Changes in hemodynamics, electrophysiology, and cardiac energy liberation were observed. The effects of histaminic and antihistaminic drugs on these changes were also studied. After two infusions of charcoal suspension, acute right ventricular overloading was recognized hemodynamically and electrophysiologically. Mitochondria isolated from both ventricles exhibited uncoupling of oxidative phosphorylation polarographically. These changes were enhanced with histamine injection and reduced with diphenhydramine injection. Histamine was seen to have some uncoupling effects on the heart mitochondria and a slight effect on cardiac dynamics. It is concluded that oxidative phosphorylation of the heart mitochondria was uncoupled in the acute stage of experimental pulmonary embolism, and that histamine might emphasize this change directly or indirectly or both, that is, directly affecting the myocardial cell metabolism, and indirectly aggravating myocardial hypoxia through pulmonary vasoconstrictive action.

Animals↗
PubMed2000

Accumulation of defective mitochondria through delayed degradation of damaged organelles and its possible role in the ageing of post-mitotic and dividing cells.

The mitochondrial theory of ageing proposes that an accumulation of defective mitochondria is a major contributor to the cellular deterioration that underlies the ageing process. The plausibility of the mitochondrial theory depends critically upon the population dynamics of intact and mutant mitochondria in different cell types. Earlier work suggested that mutant mitochondria might have a replication advantage but failed to account for the fact that mutants accumulate faster in post-mitotic than in dividing cells. We describe a new mathematical model that allows for damaged mitochondria to replicate more slowly, which accommodates experimental evidence of impaired energy generation and a reduced proton gradient in defective mitochondria. However, this is compensated for by a slower degradation rate of damaged mitochondria than intact ones, as suggested by de Grey (1997), which gives damaged mitochondria a selective advantage and leads to a clonal expansion of damaged mitochondria. This theoretical result is important because it agrees with evidence that, during ageing, single muscle fibres are taken over by one or only a few types of mtDNA mutants. The model also shows that cell division can rejuvenate and stabilize the mitochondrial population, consistent with data that post-mitotic tissues accumulate mitochondrial damage faster than mitotically active tissues.

Cell Division↗
PubMed2005

Rearrangement of the close contact between the mitochondria and the sarcoplasmic reticulum in airway smooth muscle.

The mitochondria and the sarcoplasmic reticulum (SR) are two major intracellular calcium-storing organelles that exhibit close functional interaction with each other. Close spatial association is believed to be important for their functional interaction. In this study, we have characterized the spatial relationship between the SR and the mitochondria in porcine tracheal smooth muscle cells (TSMC) under different conditions. By examining the cross-section of unstimulated TSMC with electron microscopy, we found that 99.4 +/- 0.5% of the mitochondria seen on random cross-sections were situated within 30 nm of the SR and that 82.2 +/- 6.7% of the mitochondria were completely enveloped by the SR network. Overall, 48.0 +/- 3.5% of the mitochondrial outer membrane was within 30 nm with the SR. After stimulation of the TSMC with acetylcholine (ACh) or 80 mM [K(+)] solution 97.0 +/- 2.1% and 98.6 +/- 1.4% of the mitochondria observed were situated within 30 nm of the SR, respectively. However, the proportion of the mitochondria that was completely enveloped by the SR was significantly reduced to 12.2 +/- 5.9% in ACh-stimulated cells and 9.7 +/- 6.6% in 80 mM [K(+)] stimulated cells. The percentage of mitochondrial membrane closely associated with the SR was correspondingly lower at 10.1 +/- 1.0% during ACh stimulation and 10.8 +/- 0.9% during 80 mM [K(+)] stimulation. During smooth muscle cell stimulation, the SR appears to unwrap from the mitochondria and extend into the cytoplasm while maintaining close contact with the mitochondria over a smaller area. Such static and dynamic components of the close spatial association between the mitochondria and the SR may serve as a structural basis for the selective and efficient Ca(2+) trafficking between the two organelles in TSMC.

Acetylcholine↗
PubMed1999

Measurement of mitochondrial membrane potential using fluorescent rhodamine derivatives.

We investigated the use of rhodamine 123 (R123), tetramethylrhodamine methyl ester (TMRM), and tetramethylrhodamine ethyl ester (TMRE) as fluorescent probes to monitor the membrane potential of mitochondria. These indicator dyes are lipophilic cations accumulated by mitochondria in proportion to DeltaPsi. Upon accumulation, all three dyes exhibit a red shift in both their absorption and fluorescence emission spectra. The fluorescence intensity is quenched when the dyes are accumulated by mitochondria. These properties have been used to develop a method to dynamically monitor DeltaPsi of isolated rat heart mitochondria using a ratio fluorescence approach. All three dyes bound to the inner and outer aspects of the inner mitochondrial membrane and, as a result, were accumulated by mitochondria in a greater quantity than predicted by the Nernst equation. Binding to mitochondria was temperature-dependent and the degree of binding was in the order of TMRE > R123 > TMRM. The internal and external partition coefficients for binding were determined to correct for binding in the calculation of DeltaPsi. All three dyes suppressed mitochondrial respiratory control to some extent. Inhibition of respiration was greatest with TMRE, followed by R123 and TMRM. When used at low concentrations, TMRM did not suppress respiration. The use of these dyes and ratio fluorescence techniques affords a simple method for measurement of DeltaPsi of isolated mitochondria. We also applied this approach to the isolated perfused heart to determine whether DeltaPsi could be monitored in an intact tissue. Wavelength scanning of the surface fluorescence of the heart under various conditions after accumulation of TMRM indicated that the mitochondrial matrix-induced wavelength shift of TMRM also occurs in the heart cytosol, eliminating the use of this approach in the intact heart.

Animals↗
PubMed2005

Mitochondria as a connected population: ensuring continuity of the mitochondrial genome during plant cell dedifferentiation through massive mitochondrial fusion.

Mitochondrial fusion in plants and its role in development are poorly understood. Cultured tobacco mesophyll protoplasts provide an excellent experimental system for visualizing mitochondrial dynamics. Before protoplasts first divide, mitochondria undergo a phase of extensive elongation before fission causes an increase in number, followed by actin filament (AF)-dependent dispersion that distributes mitochondria uniformly throughout the cytoplasm. Here, by fusing protoplasts containing either green fluorescent protein- or MitoTracker-labelled mitochondria, we show that elongation results from fusion during early (4-8 h) protoplast culture. This massive mitochondrial fusion (MMF) leads to near-complete mixing of the mitochondrial population within 24 h. Staining isolated mitochondria with 4',6-diamidino-2-phenylindole (DAPI) revealed that in freshly prepared protoplasts mitochondrial nucleoids were unequally distributed, with many mitochondria failing to stain with DAPI, suggesting the presence of an incomplete mitochondrial genome. Following MMF, nucleoids were distributed evenly throughout the population, thereby ensuring continuity of the mitochondrial genome in daughter cells. Massive mitochondrial fusion appears to be specific to dedifferentiation, since it also occurs in mesophyll protoplasts of Arabidopsis and Medicago but not in protoplasts from already dedifferentiated cells such as BY-2 or callus cultures. Efficient MMF requires an inner membrane electrical gradient, cytoplasmic protein synthesis, microtubules and functional kinesin but not ATP or AFs, indicating fundamental differences from mitochondrial fusion in non-plant systems. Our studies reveal that individual mitochondria are connected over time by fusion events, a finding that allows a clearer interpretation of how novel mitochondrial genotypes develop following cell fusion, and indicates that developmentally regulated fusion ensures continuity of the mitochondrial genome.

Arabidopsis↗
PubMed2006

Changes in liver mitochondrial plasticity induced by brain tumor.

BACKGROUND: Accumulating data suggest that liver is a major target organ of systemic effects observed in the presence of a cancer. In this study, we investigated the consequences of the presence of chemically induced brain tumors in rats on biophysical parameters accounting for the dynamics of water in liver mitochondria. METHODS: Tumors of the central nervous system were induced by intraveinous administration of ethylnitrosourea (ENU) to pregnant females on the 19th day of gestation. The mitochondrial crude fraction was isolated from the liver of each animal and the dynamic parameters of total water and its macromolecule-associated fraction (structured water, H2Ost) were calculated from Nuclear Magnetic Resonance (NMR) measurements. RESULTS: The presence of a malignant brain tumor induced a loss of water structural order that implicated changes in the physical properties of the hydration shells of liver mitochondria macromolecules. This feature was linked to an increase in the membrane cholesterol content, a way to limit water penetration into the bilayer and then to reduce membrane permeability. As expected, these alterations in mitochondrial plasticity affected ionic exchanges and led to abnormal features of mitochondrial biogenesis and caspase activation. CONCLUSION: This study enlightens the sensitivity of the structured water phase in the liver mitochondria machinery to external conditions such as tumor development at a distant site. The profound metabolic and functional changes led to abnormal features of ion transport, mitochondrial biogenesis and caspase activation.

Animals↗
PubMedDate not supplied

Old players in a new role: mitochondria-associated membranes, VDAC, and ryanodine receptors as contributors to calcium signal propagation from endoplasmic reticulum to the mitochondria.

In many cell types, IP(3) and ryanodine receptor (IP(3)R/RyR)-mediated Ca(2+) mobilization from the sarcoendoplasmic reticulum (ER/SR) results in an elevation of mitochondrial matrix [Ca(2+)]. Although delivery of the released Ca(2+) to the mitochondria has been established as a fundamental signaling process, the molecular mechanism underlying mitochondrial Ca(2+) uptake remains a challenge for future studies. The Ca(2+) uptake can be divided into the following three steps: (1) Ca(2+) movement from the IP(3)R/RyR to the outer mitochondrial membrane (OMM); (2) Ca(2+) transport through the OMM; and (3) Ca(2+) transport through the inner mitochondrial membrane (IMM). Evidence has been presented that Ca(2+) delivery to the OMM is facilitated by a local coupling between closely apposed regions of the ER/SR and mitochondria. Recent studies of the dynamic changes in mitochondrial morphology and visualization of the subcellular pattern of the calcium signal provide important clues to the organization of the ER/SR-mitochondrial interface. Interestingly, key steps of phospholipid synthesis and transfer to the mitochondria have also been confined to subdomains of the ER tightly associated with the mitochondria, referred as mitochondria-associated membranes (MAMs). Through the OMM, the voltage-dependent anion channels (VDAC, porin) have been thought to permit free passage of ions and other small molecules. However, recent studies suggest that the VDAC may represent a regulated step in Ca(2+) transport from IP(3)R/RyR to the IMM. A novel proposal regarding the IMM Ca(2+) uptake site is a mitochondrial RyR that would mediate rapid Ca(2+) uptake by mitochondria in excitable cells. An overview of the progress in these directions is described in the present paper.

Animals↗
PubMed2003

The dynamic localization of the glucocorticoid receptor in rat C6 glioma cell mitochondria.

Glucocorticoids modify gene expression via the translocation of receptors from the cytosol to the nucleus following agonist-associated receptor activation. In this study, we have characterized mitochondrial glucocorticoid (GR) localization and associated translocation kinetics in the C6 mouse glioma cell line. Treatment of the cells, which were cultured in steroid-depleted culture medium, with the GR agonist dexamethasone (dex) resulted in a dramatic decrease in mitochondrial GR levels in parallel with those of the cytosolic receptor. The effect was not observed in isolated intact mitochondria suggesting that the effect is unlikely to be direct but is rather a component of the combined cellular response to GR activation. A marked stimulation of the expression of the mitochondrially-encoded cytochrome oxidase-1 (COX-1) gene was found following GR activation and its export from mitochondria. The effects were inhibited by RU486. Therefore, GR is likely to have a functional role at the level of the mitochondria within intact cells.

Animals↗
PubMed2001

Effects of desmin gene knockout on mice heart mitochondria.

In heart tissue from mice lacking the intermediate filament (IF) desmin, mitochondria show an abnormal shape and distribution (Thornell et al., 1997). In the present study we have isolated heart mitochondria from desmin null (D-/-) and control (D+/+) mice, and analyzed their composition by SDS-PAGE, immunoblotting, and enzyme measurements. We found both in vitro and in situ that the conventional kinesin, the microtubule-associated plus-end directed motor, was frequently associated with D+/+ heart mitochondria, but not with D-/- heart mitochondria, suggesting that the positioning of mitochondria in heart is a dynamic event involving the IF desmin, the molecular motor kinesin, and, most likely, the microtubules (MT) network. Furthermore, an increased capacity in energy production was found, as indicated by a threefold higher creatine kinase activity in heart mitochondria from D-/- compared to D+/+ mice. We also observed a significantly lower amount of cytochrome c in heart mitochondria from D-/- mice, and a relocalization of Bcl-2, which may indicate an apoptotic condition in the cell leading to the earlier reported pathological events, such as cardiomyocytes degeneration and calcinosis of the heart (Thornell et al., 1997).

Animals↗
PubMed1987

Dynamic compartmentation of adenine nucleotides in the mitochondrial intermembrane space of rat-heart mitochondria.

To investigate whether or not the mitochondrial intermembrane space together with the extramitochondrial space form a homogeneous pool for adenine nucleotides, rat-heart mitochondria were studied in reconstituted systems with pyruvate kinase and ADP-producing enzymes with varied localization. In the hexokinase system, ADP is produced extramitochondrially by added yeast hexokinase, whereas in the creatine kinase system mitochondrial creatine kinase is responsible for ADP regeneration in the intermembrane space. The dependence of mitochondrial respiration on the extramitochondrial [ATP]/[ADP] ratio in both systems was investigated experimentally and by means of computer simulation. Near the resting state, higher [ATP]/[ADP] ratios were found in the creatine kinase system than in the hexokinase system at the same rate of respiration. This and the maintaining of a substantial creatine kinase-stimulated respiration in the presence of pyruvate kinase in excess is explained by a two-compartment model considering diffusion limitations of adenine nucleotides. A diffusion rate constant of (8.7 +/- 4.7) 10(4) microliters X mg-1 X min-1 for ADP and ATP was estimated, resulting in rate-dependent concentration differences up to 13.7 microM AdN between the extramitochondrial space and the AdN-translocator at the maximum rate of oxidative phosphorylation of rat-heart mitochondria. The results support the assumption that ADP diffusion towards the AdN-translocator is limited if its extramitochondrial concentration is low, resulting in a dynamic compartmentation of adenine nucleotides in the mitochondrial intermembrane space.

Adenine Nucleotides↗
PubMed2000

Inositol 1,4,5-trisphosphate directs Ca(2+) flow between mitochondria and the Endoplasmic/Sarcoplasmic reticulum: a role in regulating cardiac autonomic Ca(2+) spiking.

The signaling role of the Ca(2+) releaser inositol 1,4, 5-trisphosphate (IP(3)) has been associated with diverse cell functions. Yet, the physiological significance of IP(3) in tissues that feature a ryanodine-sensitive sarcoplasmic reticulum has remained elusive. IP(3) generated by photolysis of caged IP(3) or by purinergic activation of phospholipase Cgamma slowed down or abolished autonomic Ca(2+) spiking in neonatal rat cardiomyocytes. Microinjection of heparin, blocking dominant-negative fusion protein, or anti-phospholipase Cgamma antibody prevented the IP(3)-mediated purinergic effect. IP(3) triggered a ryanodine- and caffeine-insensitive Ca(2+) release restricted to the perinuclear region. In cells loaded with Rhod2 or expressing a mitochondria-targeted cameleon and TMRM to monitor mitochondrial Ca(2+) and potential, IP(3) induced transient Ca(2+) loading and depolarization of the organelles. These mitochondrial changes were associated with Ca(2+) depletion of the sarcoplasmic reticulum and preceded the arrest of cellular Ca(2+) spiking. Thus, IP(3) acting within a restricted cellular region regulates the dynamic of calcium flow between mitochondria and the endoplasmic/sarcoplasmic reticulum. We have thus uncovered a novel role for IP(3) in excitable cells, the regulation of cardiac autonomic activity.

Adenosine Triphosphate↗