‘Mild mitochondrial uncoupling’ induced protection against neuronal excitotoxicity requires AMPK activity

The preconditioning response conferred by a mild uncoupling of the mitochondrial membrane potential (Δψ_m) has been attributed to altered reactive oxygen species (ROS) production and mitochondrial Ca^2 + uptake within the cells. Here we have explored if altered cellular energetics in response to a mild mitochondrial uncoupling stimulus may also contribute to the protection. The addition of 100 nM FCCP for 30 min to cerebellar granule neurons (CGNs) induced a transient depolarization of the Δψ_m, that was sufficient to significantly reduce CGN vulnerability to the excitotoxic stimulus, glutamate. On investigation, the mild mitochondrial ‘uncoupling’ stimulus resulted in a significant increase in the plasma membrane levels of the glucose transporter isoform 3, with a hyperpolarisation of Δψ_m and increased cellular ATP levels also evident following the washout of FCCP. Furthermore, the phosphorylation state of AMP-activated protein kinase (AMPK) (Thr 172) was increased within 5 min of the uncoupling stimulus and elevated up to 1 h after washout. Significantly, the physiological changes and protection evident after the mild uncoupling stimulus were lost in CGNs when AMPK activity was inhibited. This study identifies an additional mechanism through which protection is mediated upon mild mitochondrial uncoupling: it implicates increased AMPK signalling and an adaptive shift in energy metabolism as mediators of the preconditioning response associated with FCCP-induced mild mitochondrial uncoupling.     

Inborn errors of complex II--unusual human mitochondrial diseases.

The succinate dehydrogenase consists of only four subunits, all nuclearly encoded, and is part of both the respiratory chain and the Krebs cycle. Mutations in the four genes encoding the subunits of the mitochondrial respiratory chain succinate dehydrogenase have been recently reported in human and shown to be associated with a wide spectrum of clinical presentations. Although a comparatively rare deficiency in human, molecularly defined succinate dehydrogenase deficiency has already been found to cause encephalomyopathy in childhood, optic atrophy or tumor in adulthood. Because none of the typical housekeeping genes encoding this respiratory chain complex is known to present tissue-specific isoforms, the tissue-specific involvement represents a quite intriguing question, which is mostly addressed in this review. A differential impairment of electron flow through the respiratory chain, handling of oxygen, and/or metabolic blockade possibly associated with defects in the different subunits that can be advocated to account for tissue-specific involvement is discussed.     

Archaeal complex II: 'classical' and 'non-classical' succinate:quinone reductases with unusual features.

Reversible succinate dehydrogenase (SDH) activities have been ubiquitously detected in organisms from the three domains of life. They represent constituents either of respiratory complexes II in aerobes, or of fumarate dehydrogenase complexes in anaerobes. The present review gives a survey on archaeal succinate:quinone oxidoreductases (SQRs) analyzed so far. Though some of these could be studied in detail enzymologically and spectroscopically, the existence of others has been deduced only from published genome sequences. Interestingly, two groups of enzyme complexes can be distinguished in Archaea. One group resembles the properties of SDHs known from bacteria and mitochondria. The other represents a novel class with an unusual iron-sulfur cluster in subunit B and atypical sequence motifs in subunit C which may influence electron transport mechanisms and pathways. This novel class of SQRs is discussed in comparison to the so-called 'classical' complexes. A phylogenetic analysis is presented suggesting a co-evolution of the flavoprotein-binding subunit A and subunit B containing the three iron-sulfur clusters.     

Environment versus dispersal in the assembly of western Amazonian palm communities

Aim It is a central issue in ecology and biogeography to understand what governs community assembly and the maintenance of biodiversity in tropical rain forest ecosystems. A key question is the relative importance of environmental species sorting (niche assembly) and dispersal limitation (dispersal assembly), which we investigate using a large dataset from diverse palm communities. Location Lowland rain forest, western Amazon River Basin, Peru. Methods We inventoried palm communities, registering all palm individuals and recording environmental conditions in 149 transects of 5 m × 500 m. We used ordination, Mantel tests and indicator species analysis (ISA) to assess compositional patterns, species responses to geographical location and environmental factors. Mantel tests were used to assess the relative importance of geographical distance (as a proxy for dispersal limitation) and environmental differences as possible drivers of dissimilarity in palm species composition. We repeated the Mantel tests for subsets of species that differ in traits of likely importance for habitat specialization and dispersal (height and range size). Results We found a strong relationship between compositional dissimilarity and environmental distance and a weaker but also significant relationship between compositional dissimilarity and geographical distance. Consistent with expectations, relationships with environmental and geographical distance were stronger for understorey species than for canopy species. Geographical distance had a higher correlation with compositional dissimilarity for small‐ranged species compared with large‐ranged species, whereas the opposite was true for environmental distance. The main environmental correlates were inundation and soil nutrient levels. Main conclusions The assembly of palm communities in the western Amazon appears to be driven primarily by species sorting according to hydrology and soil, but with dispersal limitation also playing an important role. The importance of environmental characteristics and geographical distance varies depending on plant height and geographical range size in agreement with functional predictions, increasing our confidence in the inferred assembly mechanisms.     

Contents of polyamines during vernalization in wheat and the effect of zearalenone

The contents of endogenous free and conjugated polyamines, putrescine (Put) and spermidine (Spd), were determined during 9 week of vernalization (at 5 °C) in winter wheat seedlings cultivated on Murashige and Skoog media without (MS0) and with 2 mg dm⁻³ zearalenone (MSZEN). At the 4^th week of chilling treatment, which is sufficient to induce generative development in 30 % of plants, the marked increase in free and conjugated forms of Put and free Spd were observed. The presence of ZEN in medium significantly accelerated the vernalization. About 20 % of plants treated with ZEN flowered already after 2 weeks and 40 % after 3 weeks of chilling. Significantly higher content of free Put was determined in roots grown on MSZEN compared with MS0 during the first 5 weeks of vernalization with maximum at the 4^th week. After germination, a marked decrease in free Spd content was observed both in plants grown on MS0 and MSZEN. Application of ZEN significantly slowed down the Spd decline in leaves and roots during the first and second week of vernalization. The content of Spd and its conjugates decreased in vernalized plants after 1 week of cultivation at 20 °C.     

Thrombopoietic activity induced by blood withdrawal and administration of antithrombocyte serum in nephrectomized rats. Role of kidneys in the production of thrombopoietin

The thrombopoietic serum activity was examined in rats during thrombocytopenia produced by bleeding or after treatment with antithrombocyte serum (ATS). 6 hours after both treatments the thrombopoietic activity of the serum, i.e. its content of thrombopoietin, is increased. After the ATS treatment of nephrectomized animals a similar increase of thrombopoietic activity as in normal animals could be achieved. In contrast to that, no similar increase of thrombopoietic activity was observed in nephrectomized animals after blood loss. According to the results of the authors the increase of thrombopoietic activity produced by different stimuli can be attributed to different mechanisms.     

Effect of lidocaine and pyromecaine on the size of an experimental myocardial infarct

The experiments on rats with a 3-day myocardial infarction caused by the left coronary artery ligation have shown that multiple lidocaine and pyromecaine injections according to a given scheme decrease the size of the necrosis area. Drug effects were not related to their action on the blood supply of the ischemic area.     

Reasons for disorders of fatty acid oxidation in isolated heart mitochondria during ischemia

The influence of malate and cytochrome c on fatty acid oxidation under control and ischemic conditions was investigated. In the medium without malate, cytochrome did not make fatty acid oxidation decreased during ischemia return to normal. Oxidation in the media containing malate and cytochrome did not differ from control only when it was measured after preliminary oxidation of endogenous substrates. The ratio of palmitoyl-CoA and palmitoyl carnitine to the respiration rates at state 3 was unchanged at 60 min ischemia. Apparently, no changes in carnitine acyltransferase playing a role in oxidation of palmitoyl-CoA took place. Thus, the decrease of fatty acid oxidation at early periods of ischemia is largely caused by a reduction in the content of cytochrome c and intermediates of Krebs cycle in the mitochondria.