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Mitochondrial Morphology (mitochondrial + morphology)
Selected AbstractsComplex patterns of mitochondrial dynamics in human pancreatic cells revealed by fluorescent confocal imagingJOURNAL OF CELLULAR AND MOLECULAR MEDICINE, Issue 1-2 2010Andrey V. Kuznetsov Abstract Mitochondrial morphology and intracellular organization are tightly controlled by the processes of mitochondrial fission,fusion. Moreover, mitochondrial movement and redistribution provide a local ATP supply at cellular sites of particular demands. Here we analysed mitochondrial dynamics in isolated primary human pancreatic cells. Using real time confocal microscopy and mitochondria-specific fluorescent probes tetramethylrhodamine methyl ester and MitoTracker Green we documented complex and novel patterns of spatial and temporal organization of mitochondria, mitochondrial morphology and motility. The most commonly observed types of mitochondrial dynamics were (i) fast fission and fusion; (ii) small oscillating movements of the mitochondrial network; (iii) larger movements, including filament extension, retraction, fast (0.1,0.3 ,m/sec.) and frequent oscillating (back and forth) branching in the mitochondrial network; (iv) as well as combinations of these actions and (v) long-distance intracellular translocation of single spherical mitochondria or separated mitochondrial filaments with velocity up to 0.5 ,m/sec. Moreover, we show here for the first time, a formation of unusual mitochondrial shapes like rings, loops, and astonishingly even knots created from one or more mitochondrial filaments. These data demonstrate the presence of extensive heterogeneity in mitochondrial morphology and dynamics in living cells under primary culture conditions. In summary, this study reports new patterns of morphological changes and dynamic motion of mitochondria in human pancreatic cells, suggesting an important role of integrations of mitochondria with other intracellular structures and systems. [source] Mitochondrial morphology transition is an early indicator of subsequent cell death in ArabidopsisNEW PHYTOLOGIST, Issue 1 2008Iain Scott Summary ,,Mitochondrial morphology and dynamics were investigated during the onset of cell death in Arabidopsis thaliana. Cell death was induced by either chemical (reactive oxygen species (ROS)) or physical (heat) shock. ,,Changes in mitochondrial morphology in leaf tissue, or isolated protoplasts, each expressing mitochondrial-targeted green fluorescent protein (GFP), were observed by epifluorescence microscopy, and quantified. ,,Chemical induction of ROS production, or a mild heat shock, caused a rapid and consistent change in mitochondrial morphology (termed the mitochondrial morphology transition) that preceded cell death. Treatment of protoplasts with a cell-permeable superoxide dismutase analogue, TEMPOL, blocked this morphology change. Incubation of protoplasts in micromolar concentrations of the calcium channel-blocker lanthanum chloride, or the permeability transition pore inhibitor cyclosporin A, prevented both the mitochondrial morphology transition and subsequent cell death. ,,It is concluded that the observed mitochondrial morphology transition is an early and specific indicator of cell death and is a necessary component of the cell death process. [source] Deletion of mdmB impairs mitochondrial distribution and morphology in Aspergillus nidulansCYTOSKELETON, Issue 2 2003Katrin V. Koch Abstract Mitochondria form a dynamic network of interconnected tubes in the cells of Saccharomyces cerevisiae or filamentous fungi such as Aspergillus nidulans,Neurospora crassa, or Podospora anserina. The dynamics depends on the separation of mitochondrial fragments, their movement throughout the cell, and their subsequent fusion with the other parts of the organelle. Interestingly, the microtubule network is required for the distribution in N. crassa and S. pombe, while S. cerevisiae and A. nidulans appear to use the actin cytoskeleton. We studied a homologue of S. cerevisiae Mdm10 in A. nidulans, and named it MdmB. The open reading frame is disrupted by two introns, one of which is conserved in mdm10 of P. anserina. The MdmB protein consists of 428 amino acids with a predicted molecular mass of 46.5 kDa. MdmB shares 26% identical amino acids to Mdm10 from S. cerevisiae, 35% to N. crassa, and 32% to the P. anserina homologue. A MdmB-GFP fusion protein co-localized evenly distributed along mitochondria. Extraction of the protein was only possible after treatment with a non-ionic and an ionic detergent (1% Triton X-100; 0.5% SDS) suggesting that MdmB was tightly bound to the mitochondrial membrane fraction. Deletion of the gene in A. nidulans affected mitochondrial morphology and distribution at 20°C but not at 37°C. mdmB deletion cells contained two populations of mitochondria at lower temperature, the normal tubular network plus some giant, non-motile mitochondria. Cell Motil. Cytoskeleton 55:114,124, 2003. © 2003 Wiley-Liss, Inc. [source] Helicobacter Hypothesis for Idiopathic Parkinsonism: Before and BeyondHELICOBACTER, Issue 5 2008R. John Dobbs Abstract We challenge the concept of idiopathic parkinsonism (IP) as inevitably progressive neurodegeneration, proposing a natural history of sequential microbial insults with predisposing host response. Proof-of-principle that infection can contribute to IP was provided by case studies and a placebo-controlled efficacy study of Helicobacter eradication. "Malignant" IP appears converted to "benign", but marked deterioration accompanies failure. Similar benefit on brady/hypokinesia from eradicating "low-density" infection favors autoimmunity. Although a minority of UK probands are urea breath test positive for Helicobacter, the predicted probability of having the parkinsonian label depends on the serum H. pylori antibody profile, with clinically relevant gradients between this "discriminant index" and disease burden and progression. In IP, H. pylori antibodies discriminate for persistently abnormal bowel function, and specific abnormal duodenal enterocyte mitochondrial morphology is described in relation to H. pylori infection. Slow intestinal transit manifests as constipation from the prodrome. Diarrhea may flag secondary small-intestinal bacterial overgrowth. This, coupled with genetically determined intense inflammatory response, might explain evolution from brady/hypokinetic to rigidity-predominant parkinsonism. [source] Mitochondrial Oxidative Stress Plays a Key Role in Aging and ApoptosisIUBMB LIFE, Issue 5 2000Juan Sastre Abstract Harman first suggested in 1972 that mitochondria might be the biological clock in aging, noting that the rate of oxygen consumption should determine the rate of accumulation of mitochondrial damage produced by free radical reactions. Later in 1980 Miquel and coworkers proposed the mitochondrial theory of cell aging. Mitochondria from postmitotic cells use O2 at a high rate, hence releasing oxygen radicals that exceed the cellular antioxidant defences. The key role of mitochondria in cell aging has been outlined by the degeneration induced in cells microinjected with mitochondria isolated from fibroblasts of old rats, especially by the inverse relationship reported between the rate of mitochondrial production of hydroperoxide and the maximum life span of species. An important change in mitochondrial lipid composition is the age-related decrease found in cardiolipin content. The concurrent enhancement of lipid peroxidation and oxidative modification of proteins in mitochondria further increases mutations and oxidative damage to mitochondrial DNA (mtDNA) in the aging process. The respiratory enzymes containing the defective mtDNA-encoded protein subunits may increase the production of reactive oxygen species, which in turn would aggravate the oxidative damage to mitochondria. Moreover, superoxide radicals produced during mitochondrial respiration react with nitric oxide inside mitochondria to yield damaging peroxynitrite. Treatment with certain antioxidants, such as sulphur-containing antioxidants, vitamins C and E, or the Ginkgo biloba extract EGb 761, protects against the ageassociated oxidative damage to mtDNA and the oxidation of mitochondrial glutathione. Moreover, the EGb 761 extract also prevents changes in mitochondrial morphology and function associated with aging of the brain and liver. [source] Complex patterns of mitochondrial dynamics in human pancreatic cells revealed by fluorescent confocal imagingJOURNAL OF CELLULAR AND MOLECULAR MEDICINE, Issue 1-2 2010Andrey V. Kuznetsov Abstract Mitochondrial morphology and intracellular organization are tightly controlled by the processes of mitochondrial fission,fusion. Moreover, mitochondrial movement and redistribution provide a local ATP supply at cellular sites of particular demands. Here we analysed mitochondrial dynamics in isolated primary human pancreatic cells. Using real time confocal microscopy and mitochondria-specific fluorescent probes tetramethylrhodamine methyl ester and MitoTracker Green we documented complex and novel patterns of spatial and temporal organization of mitochondria, mitochondrial morphology and motility. The most commonly observed types of mitochondrial dynamics were (i) fast fission and fusion; (ii) small oscillating movements of the mitochondrial network; (iii) larger movements, including filament extension, retraction, fast (0.1,0.3 ,m/sec.) and frequent oscillating (back and forth) branching in the mitochondrial network; (iv) as well as combinations of these actions and (v) long-distance intracellular translocation of single spherical mitochondria or separated mitochondrial filaments with velocity up to 0.5 ,m/sec. Moreover, we show here for the first time, a formation of unusual mitochondrial shapes like rings, loops, and astonishingly even knots created from one or more mitochondrial filaments. These data demonstrate the presence of extensive heterogeneity in mitochondrial morphology and dynamics in living cells under primary culture conditions. In summary, this study reports new patterns of morphological changes and dynamic motion of mitochondria in human pancreatic cells, suggesting an important role of integrations of mitochondria with other intracellular structures and systems. [source] Acetyl -l- carnitine protects yeast cells from apoptosis and aging and inhibits mitochondrial fissionAGING CELL, Issue 4 2010Vanessa Palermo Summary In this work we report that carnitines, in particular acetyl -l- carnitine (ALC), are able to prolong the chronological aging of yeast cells during the stationary phase. Lifespan extension is significantly reduced in yca1 mutants as well in rho0 strains, suggesting that the protective effects pass through the Yca1 caspase and mitochondrial functions. ALC can also prevent apoptosis in pro-apoptotic mutants, pointing to the importance of mitochondrial functions in regulating yeast apoptosis and aging. We also demonstrate that ALC attenuates mitochondrial fission in aged yeast cells, indicating a correlation between its protective effect and this process. Our findings suggest that ALC, used as therapeutic for stroke, myocardial infarction and neurodegenerative diseases, besides the well-known anti-oxidant effects, might exert protective effects also acting on mitochondrial morphology. [source] Chronic exposure to sub-lethal beta-amyloid (A,) inhibits the import of nuclear-encoded proteins to mitochondria in differentiated PC12 cells*JOURNAL OF NEUROCHEMISTRY, Issue 5 2007Daniel Sirk Abstract Studies on amyloid beta (A,|), the peptide thought to play a crucial role in the pathogenesis of Alzheimer's disease, have implicated mitochondria in A,-mediated neurotoxicity. We used differentiated PC12 cells stably transfected with an inducible green fluorescent protein (GFP) fusion protein containing an N,-terminal mitochondrial targeting sequence (mtGFP), to examine the effects of sub-lethal A, on the import of nuclear-encoded proteins to mitochondria. Exposure to sub-lethal A,25,35 (10 ,mol/L) for 48 h inhibited mtGFP import to mitochondria; average rates decreased by 20 ± 4%. Concomitant with the decline in mtGFP, cytoplasmic mtGFP increased significantly while mtGFP expression and intramitochondrial mtGFP turnover were unchanged. Sub-lethal A,1,42 inhibited mtGFP import and increased cytoplasmic mtGFP but only after 96 h. The import of two endogenous nuclear-encoded mitochondrial proteins, mortalin/mtHsp70 and Tom20 also declined. Prior to the decline in import, mitochondrial membrane potential (mmp), and reactive oxygen species levels were unchanged in A,-treated cells versus reverse phase controls. Sustained periods of decreased import were associated with decreased mmp, increased reactive oxygen species, increased vulnerability to oxygen-glucose deprivation and altered mitochondrial morphology. These findings suggest that an A,-mediated inhibition of mitochondrial protein import, and the consequent mitochondrial impairment, may contribute to Alzheimer's disease. [source] Uncoupling of intestinal mitochondrial oxidative phosphorylation and inhibition of cyclooxygenase are required for the development of NSAID-enteropathy in the ratALIMENTARY PHARMACOLOGY & THERAPEUTICS, Issue 5 2000Somasundaram Background: The pathogenesis of NSAID-induced gastrointestinal damage is believed to involve a nonprostaglandin dependent effect as well as prostaglandin dependent effects. One suggestion is that the nonprostaglandin mechanism involves uncoupling of mitochondrial oxidative phosphorylation. Aims: To assess the role of uncoupling of mitochondrial oxidative phosphorylation in the pathogenesis of small intestinal damage in the rat. Methods: We compared key pathophysiologic events in the small bowel following (i) dinitrophenol, an uncoupling agent (ii) parenteral aspirin, to inhibit cyclooxygenase without causing a ,topical' effect and (iii) the two together, using (iv) indomethacin as a positive control. Results: Dinitrophenol altered intestinal mitochondrial morphology, increased intestinal permeability and caused inflammation without affecting gastric permeability or intestinal prostanoid levels. Parenteral aspirin decreased mucosal prostanoids without affecting intestinal mitochondria in vivo, gastric or intestinal permeability. Aspirin caused no inflammation or ulcers. When dinitrophenol and aspirin were given together the changes in intestinal mitochondrial morphology, permeability, inflammation and prostanoid levels and the macro- and microscopic appearances of intestinal ulcers were similar to indomethacin. Conclusions: These studies allow dissociation of the contribution and consequences of uncoupling of mitochondrial oxidative phosphorylation and cyclooxygenase inhibition in the pathophysiology of NSAID enteropathy. While uncoupling of enterocyte mitochondrial oxidative phosphorylation leads to increased intestinal permeability and low grade inflammation, concurrent decreases in mucosal prostanoids appear to be important in the development of ulcers. [source] Htd2p/Yhr067p is a yeast 3-hydroxyacyl-ACP dehydratase essential for mitochondrial function and morphologyMOLECULAR MICROBIOLOGY, Issue 5 2004Alexander J. Kastaniotis Summary Among the recently recognized aspects of mitochondrial functions, in yeast as well as humans, is their ability to synthesize fatty acids in a malonyl-CoA dependent manner. We describe here the identification of the 3-hydroxyacyl-ACP dehydratase involved in mitochondrial fatty acid synthesis. A colony-colour-sectoring screen was applied in Saccharomyces cerevisiae in a search for mutants that, when grown on a non-fermentable carbon source, were unable to lose a plasmid that carried a chimeric construct coding for mitochondrially localized bacterial analogue. Our mutants, which are respiratory deficient, lack cytochromes and display abnormal mitochondrial morphology,, were, found, to, have, a lesion in the yeast YHR067w/RMD12 gene. The Yhr067p is predicted to be a member of the thioesterase/thioester dehydratase-isomerase superfamily enzymes. Hydratase 2 activity in mitochondrial extracts from cells overexpressing YHR067w was increased. These overexpressing cells also display a striking mitochondrial enlargement phenotype. We conclude that YHR067w encodes a novel mitochondrial 3- hydroxyacyl- thioester dehydratase 2 and suggest renaming it HTD2. The mitochondrial phenotypes of the null and overexpression mutants suggest a crucial role of YHR067w in maintenance of mitochondrial respiratory competence and morphology in yeast. [source] Mitochondrial morphology transition is an early indicator of subsequent cell death in ArabidopsisNEW PHYTOLOGIST, Issue 1 2008Iain Scott Summary ,,Mitochondrial morphology and dynamics were investigated during the onset of cell death in Arabidopsis thaliana. Cell death was induced by either chemical (reactive oxygen species (ROS)) or physical (heat) shock. ,,Changes in mitochondrial morphology in leaf tissue, or isolated protoplasts, each expressing mitochondrial-targeted green fluorescent protein (GFP), were observed by epifluorescence microscopy, and quantified. ,,Chemical induction of ROS production, or a mild heat shock, caused a rapid and consistent change in mitochondrial morphology (termed the mitochondrial morphology transition) that preceded cell death. Treatment of protoplasts with a cell-permeable superoxide dismutase analogue, TEMPOL, blocked this morphology change. Incubation of protoplasts in micromolar concentrations of the calcium channel-blocker lanthanum chloride, or the permeability transition pore inhibitor cyclosporin A, prevented both the mitochondrial morphology transition and subsequent cell death. ,,It is concluded that the observed mitochondrial morphology transition is an early and specific indicator of cell death and is a necessary component of the cell death process. [source] Chemical induction of rapid and reversible plastid filamentation in Arabidopsis thaliana rootsPHYSIOLOGIA PLANTARUM, Issue 2 2010Ryuuichi D. Itoh Plastids assume various morphologies depending on their developmental status, but the basis for developmentally regulated plastid morphogenesis is poorly understood. Chemical induction of alterations in plastid morphology would be a useful tool for studying this; however, no such chemicals have been identified. Here, we show that antimycin A, an effective respiratory inhibitor, can change plastid morphology rapidly and reversibly in Arabidopsis thaliana. In the root cortex, hypocotyls, cotyledon epidermis and true leaf epidermis, significant differences in mitochondrial morphology were not observed between antimycin-treated and untreated tissues. In contrast, antimycin caused extreme filamentation of plastids in the mature cortices of main roots. This phenomenon was specifically observed in the mature root cortex. Other mitochondrial respiratory inhibitors (rotenone and carbonyl cyanide m -chlorophenylhydrazone), hydrogen peroxide, S -nitroso- N -acetylpenicillamine [a nitric oxide (NO) donor] and 3-(3,4-dichlorophenyl)-1,1-dimethylurea did not mimic the phenomenon under the present study conditions. Antimycin-induced plastid filamentation was initiated within 5 min after the onset of chemical treatment and appeared to complete within 1 h. Plastid morphology was restored within 7 h after the washout of antimycin, suggesting that the filamentation was reversible. Co-applications of antimycin and cytoskeletal inhibitors (demecolcine or latrunculin B) or protein synthesis inhibitors (cycloheximide or chloramphenicol) still caused plastid filamentation. Antimycin A was also effective for plastid filamentation in the chloroplast division mutants atftsZ1-1 and atminE1. Salicylhydroxamic acid, an alternative oxidase inhibitor, was solely found to suppress the filamentation, implying the possibility that this phenomenon was partly mediated by an antimycin-activated alternative oxidase in the mitochondria. [source] Interactions between CB1 receptors and TRPV1 channels mediated by 12-HPETE are cytotoxic to mesencephalic dopaminergic neuronsBRITISH JOURNAL OF PHARMACOLOGY, Issue 2 2008S R Kim Background and purposes: We recently proposed the existence of neurotoxic interactions between the cannabinoid type 1 (CB1) receptor and transient receptor potential vanilloid 1 (TRPV1) channels in rat mesencephalic cultures. This study seeks evidence for the mediator(s) and mechanisms underlying the neurotoxic interactions between CB1 receptors and TRPV1 in vitro and in vivo. Experimental approach: The mediator(s) and mechanism(s) for the interactions between CB1 receptors and TRPV1 were evaluated by cell viability assays, immunocytochemistry, Fura-2 calcium imaging, mitochondrial morphology assay, ELISA and Western blot assay in vitro in neuron-enriched mesencephalic cultures. Injections into the substantia nigra and subsequent cell counts were also used to confirm these interactions in vivo. Key results: The neurotoxic interactions were mediated by 12(S)-hydroperoxyeicosatetraenoic acid (12(S)-HPETE), an endogenous TRPV1 agonist. CB1 receptor agonists (HU210 and WIN55,212-2) increased the level of 12(S)-hydroxyeicosatetraenoic acid (12(S)-HETE), a downstream metabolite of 12(S)-HPETE, which stimulates TRPV1-mediated death of mesencephalic neurons, both in vitro and in vivo. The neurotoxicity was mediated by increased intracellular Ca2+ concentration ([Ca2+]i) through TRPV1, consequently leading to mitochondrial damage and was attenuated by baicalein, a 12-lipoxygenase inhibitor. Conclusion and implications: Activation of CB1 receptors in rat mesencephalic neurons was associated with biosynthesis of 12(S)-HPETE, which in turn stimulated TRPV1 activity, leading to increased [Ca2+]i, mitochondrial damage and neuronal death. British Journal of Pharmacology (2008) 155, 253,264; doi:10.1038/bjp.2008.246; published online 16 June 2008 [source] | |||||||||||||||||||||||||