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981.
Emelie Braschi Heidi M. McBride 《BioEssays : news and reviews in molecular, cellular and developmental biology》2010,32(11):958-966
As endosymbionts, the mitochondria are unique among organelles. This review provides insights into mitochondrial behavior and introduces the idea of a unified collective, an interconnected reticulum reminiscent of the Borg, a fictional humanoid species from the Star Trek television series whereby decisions are made within their network (or “hive”), linked to signaling cascades that coordinate the cross‐talk between mitochondrial and cellular processes (“subspace domain”). Similarly, mitochondrial dynamics are determined by two distinct processes, namely the local regulation of fission/fusion and the global control of their behavior through cellular signaling pathways. Indeed, decisions within the hive provide each mitochondrial unit with autonomous control of their own degradation, whereby mitochondrial fusion is inactivated and they become substrates for autophagy. Decisions within the subspace domain couple signaling pathways involved in the functional integration of mitochondria with complex cellular transitions, including developmental cues, mitosis, and apoptosis. 相似文献
982.
Hiroshi Shiraishi Hideaki Okamoto Hiromitsu Hara Hiroki Yoshida 《Biochimica et Biophysica Acta (BBA)/General Subjects》2010
Background
Various forms of cell death, such as apoptotic, autophagic and non-lysosomal types, are implicated in normal physiological processes. Apoptotic protease activating factor 1 (Apaf1) is an important component of the intrinsic apoptotic pathway. Deficiency of Apaf1 results in an accumulation of neural progenitor cells (NPCs) in the developing central nervous system and thus, in perinatal lethality. A small percentage of the mutant mice, however, are viable and grow to maturity. The occurrence of such normal mutants implicates alternative cell death pathways during neurogenesis.Methods
NPCs prepared from wild-type or Apaf1-deficient embryos were cultured in growth factor-deprived medium and examined for cell death, caspase activation and morphological alterations. Generation of reactive oxygen species (ROS) and the effects of antioxidants were examined.Results
Wild-type NPCs underwent apoptosis within 24 hours of withdrawal of epidermal growth factor (EGF) or insulin, whereas Apaf1-deficient NPCs underwent cell death but showed no signs of apoptosis. Autophagy was not necessarily accompanied by cell death. Cell death of the Apaf1-deficient NPCs resembled necroptosis—necrosis-like programmed cell death. The necroptosis inhibitor necrostatin-1, however, failed to inhibit the cell death. ROS accumulation was detected in NPCs deprived of growth factors, and an antioxidant partially suppressed the non-apoptotic cell death of Apaf1-deficient NPCs.Conclusions
These data indicate that after withdrawal EGF or insulin withdrawal, the Apaf1-deficient cells underwent non-apoptotic cell death. ROS generation may partially participate in the cell death.General Significance
Non-apoptotic cell death in NPCs may be a compensatory mechanism in the developing CNS of Apaf1-deficient embryos. 相似文献983.
Xiantao Li Markus Rapedius Thomas Baukrowitz Gong Xin Liu D.K. Srivastava Jürgen Daut Peter J. Hanley 《Biochimica et Biophysica Acta (BBA)/General Subjects》2010
Background
5-Hydroxydecanoate (5-HD) inhibits preconditioning, and it is assumed to be a selective inhibitor of mitochondrial ATP-sensitive K+ (mitoKATP) channels. However, 5-HD is a substrate for mitochondrial outer membrane acyl-CoA synthetase, which catalyzes the reaction: 5?HD + CoA + ATP → 5-HD-CoA (5-hydroxydecanoyl-CoA) + AMP + pyrophosphate. We aimed to determine whether the reactants or principal product of this reaction modulate sarcolemmal KATP (sarcKATP) channel activity.Methods
Single sarcKATP channel currents were measured in inside-out patches excised from rat ventricular myocytes. In addition, sarcKATP channel activity was recorded in whole-cell configuration or in giant inside-out patches excised from oocytes expressing Kir6.2/SUR2A.Results
5-HD inhibited (IC50 ∼ 30 μM) KATP channel activity, albeit only in the presence of (non-inhibitory) concentrations of ATP. Similarly, when the inhibitory effect of 0.2 mM ATP was reversed by 1 μM oleoyl-CoA, subsequent application of 5-HD blocked channel activity, but no effect was seen in the absence of ATP. Furthermore, we found that 1 μM coenzyme A (CoA) inhibited sarcKATP channels. Using giant inside-out patches, which are weakly sensitive to “contaminating” CoA, we found that Kir6.2/SUR2A channels were insensitive to 5-HD-CoA. In intact myocytes, 5-HD failed to reverse sarcKATP channel activation by either metabolic inhibition or rilmakalim.General significance
SarcKATP channels are inhibited by 5-HD (provided that ATP is present) and CoA but insensitive to 5-HD-CoA. 5-HD is equally potent at “directly” inhibiting sarcKATP and mitoKATP channels. However, in intact cells, 5-HD fails to inhibit sarcKATP channels, suggesting that mitochondria are the preconditioning-relevant targets of 5-HD. 相似文献984.
985.
Arti Parihar Mordhwaj S. Parihar Rafal Nazarewicz Pedram Ghafourifar 《Biochimica et Biophysica Acta (BBA)/General Subjects》2010
Background
Ceramides are intracellular lipid mediator implicated in various cellular responses, including oxidative stress and programmed cell death. Studies demonstrated strong links between ceramide and the mitochondria in the regulation of apoptosis. However, the mechanism of apoptosis induced by ceramides is not fully understood. The present study delineates importance of the redox state of cytochrome c for release of cytochrome c and apoptosis of human mammary adenocarcinoma MCF-7 and MDA-MB-231 cells induced by ceramides.Methods
The study uses MCF-7 and MDA-MB-231 cells, isolated mitochondria, submitochondrial particles, and oxidized and reduced cytochrome c. Methods used include flow cytometry, immunoblotting, spectroscopy, and respirometry.Results
We show that ceramides induce mitochondrial oxidative stress and release of cytochrome c from the mitochondria of these cells. Our findings show that ceramides react with oxidized cytochrome c whereas reduced cytochrome c does not react with ceramides. We also show that oxidized cytochrome c reacted with ceramides exerts lower reducibility and function to support mitochondrial respiration. Furthermore, our data show that glutathione protects cytochrome c of reacting with ceramides by increasing the reduced state of cytochrome c.Conclusions
Ceramides induce oxidative stress and apoptosis in human mammary adenocarcinoma cells by interacting with oxidized cytochrome c leading to the release of cytochrome c from the mitochondria. Our findings suggest a novel mechanism for protective role of glutathione.General significance
Our study suggests that the redox state of cytochrome c is important in oxidative stress and apoptosis induced by ceramides. 相似文献986.
Manuel Vera Martí Cortey Núria Sanz José‐Luis García‐Marín 《Journal of Zoological Systematics and Evolutionary Research》2010,48(2):181-187
The Iberian Peninsula contains diverse populations of freshwater fish, with major river basins comprising differentiated biogeographic units. The Duero River flows through the North‐Western Iberian Peninsula and is one of the most important rivers within the Iberian glacial refuge. Brown trout (Salmo trutta) populate this whole basin, and studies using both allozyme and microsatellite loci have detected a geographically sorted distribution of genetic variation in this species. In this work, sequences of the mitochondrial control region obtained from 299 brown trout from the Duero River were compared with other Iberian and European datasets. Two differentiated haplotype groups were detected inside the Duero River basin. One of them was related to the Atlantic (AT) lineage that is present in Northern European populations, whereas the other comprised an unique group that was restricted to the inner region of the basin. The amount of divergence of this Duero group from the other brown trout populations studied is consistent with a new trout lineage (Duero, DU) that is endemic to this river basin and that diverged from other Atlantic populations during the Pleistocene. The distribution of the DU and AT quaternary lineages in the Duero River was consistent with the ichthyological pattern described in the basin that originated during the Miocene–Pliocene. Evidence of selective processes that favour the haplotypes of the DU lineage may explain this discrepancy. 相似文献
987.
988.
MERYL C. MIMS C. DARRIN HULSEY BENJAMIN M. FITZPATRICK J. TODD STREELMAN 《Molecular ecology》2010,19(5):940-951
Phenotypically diverse Lake Malawi cichlids exhibit similar genomes. The extensive sharing of genetic polymorphism among forms has both intrigued and frustrated biologists trying to understand the nature of diversity in this and other rapidly evolving systems. Shared polymorphism might result from hybridization and/or the retention of ancestrally polymorphic alleles. To examine these alternatives, we used new genomic tools to characterize genetic differentiation in widespread, geographically structured populations of Labeotropheus fuelleborni and Metriaclima zebra. These phenotypically distinct species share mitochondrial DNA (mtDNA) haplotypes and show greater mtDNA differentiation among localities than between species. However, Bayesian analysis of nuclear single nucleotide polymorphism (SNP) data revealed two distinct genetic clusters corresponding perfectly to morphologically diagnosed L. fuelleborni and M. zebra. This result is a function of the resolving power of the multi‐locus dataset, not a conflict between nuclear and mitochondrial partitions. Locus‐by‐locus analysis showed that mtDNA differentiation between species (FCT) was nearly identical to the median single‐locus SNP FCT. Finally, we asked whether there is evidence for gene flow at sites of co‐occurrence. We used simulations to generate a null distribution for the level of differentiation between co‐occurring populations of L. fuelleborni and M. zebra expected if there was no hybridization. The null hypothesis was rejected for the SNP data; populations that co‐occur at rock reef sites were slightly more similar than expected by chance, suggesting recent gene flow. The coupling of numerous independent markers with extensive geographic sampling and simulations utilized here provides a framework for assessing the prevalence of gene flow in recently diverged species. 相似文献
989.
Kurt A. Jellinger 《Journal of cellular and molecular medicine》2010,14(3):457-487
Neurodegenerative diseases are characterized by progressive dysfunction of specific populations of neurons, determining clinical presentation. Neuronal loss is associated with extra and intracellular accumulation of misfolded proteins, the hallmarks of many neurodegenerative proteinopathies. Major basic processes include abnormal protein dynamics due to deficiency of the ubiquitin–proteosome–autophagy system, oxidative stress and free radical formation, mitochondrial dysfunction, impaired bioenergetics, dysfunction of neurotrophins, ‘neuroinflammatory’ processes and (secondary) disruptions of neuronal Golgi apparatus and axonal transport. These interrelated mechanisms lead to programmed cell death is a long run over many years. Neurodegenerative disorders are classified according to known genetic mechanisms or to major components of protein deposits, but recent studies showed both overlap and intraindividual diversities between different phenotypes. Synergistic mechanisms between pathological proteins suggest common pathogenic mechanisms. Animal models and other studies have provided insight into the basic neurodegeneration and cell death programs, offering new ways for future prevention/treatment strategies. 相似文献
990.
Hiroyuki Matsuda Yasutaka Kurata Satoshi Matsuoka Akinori Noma 《Progress in biophysics and molecular biology》2010,103(1):102-110
We aimed to study kinetics of modulation by intracellular Mg2+ of cardiac gap junction (Mg2+ gate). Paired myocytes of guinea-pig ventricle were superfused with solutions containing various concentrations of Mg2+. In order to rapidly apply Mg2+ to one aspect of the gap junction, the non-junctional membrane of one of the pair was perforated at nearly the connecting site by pulses of nitrogen laser beam. The gap junction conductance (Gj) was measured by clamping the membrane potential of the other cell using two-electrode voltage clamp method. The laser perforation immediately increased Gj, followed by slow Gj change with time constant of 3.5 s at 10 mM Mg2+. Mg2+ more than 1.0 mM attenuated dose-dependently the gap junction conductance and lower Mg2+ (0.6 mM) increased Gj with a Hill coefficient of 3.4 and a half-maximum effective concentration of 0.6 mM. The time course of Gj changes was fitted by single exponential function, and the relationship between the reciprocal of time constant and Mg2+ concentration was almost linear. Based on the experimental data, a mathematical model of Mg2+ gate with one open state and three closed states well reproduced experimental results. One-dimensional cable model of thirty ventricular myocytes connected to the Mg2+ gate model suggested a pivotal role of the Mg2+ gate of gap junction under pathological conditions. 相似文献