The mitochondrial small heat-shock protein protects NADH:ubiquinone oxidoreductase of the electron transport chain during heat stress in plants

Functional inactivation of the mitochondrial small heat-shock protein (lmw Hsp) in submitochondrial vesicles using protein-specific antibodies indicated that this protein protects NADH:ubiquinone oxidoreductase (complex I), and consequently electron transport from complex I to cytochrome c:O₂ oxidoreductase (complex IV). Lmw Hsp function completely accounted for heat acclimation of complex I electron transport in pre-heat-stressed plants. Addition of purified lmw Hsp to submitochondrial vesicles lacking this Hsp increased complex I electron transport rates 100% in submitochondrial vesicles assayed at high temperatures. These results indicate that production of the mitochondrial lmw Hsp is an important adaptation to heat stress in plants.     

海南产桶形芋螺线粒体基因组DNA提取条件的优化

提取海南产桶形芋螺线粒体基因组完整DNA (mtDNA),并对提取条件进行优化。以桶形芋螺腹足肌肉、毒腺和肝胰脏三个不同组织为材料,分别采用改进高盐沉淀法、细胞器/磁珠法和试剂盒提取三种方法,提取桶形芋螺mtDNA,并利用琼脂糖凝胶电泳和紫外分光光度计对提取mtDNA的纯度和浓度进行测定。以coxⅠ-rRNA小亚基基因和α-芋螺毒素基因设计引物,通过PCR反应来确证所提取的DNA确实是mtDNA。试剂盒法提取肝胰脏、高盐沉淀法提取肝胰脏和腹足肌肉组织这三种方法的产率很高,分别为44.4μg/mg、43.3μg/mg和32.6μg/mg。A260/280比值表明,改进高盐沉淀法提取毒腺和腹足肌肉组织,细胞器磁珠法提取腹足肌肉组织的mtDNA纯度很高。综合比较,采用改进高盐沉淀法,利用桶形芋螺腹足肌肉组织所提取的mtDNA产率高、质量好、纯度高。高质量芋螺mtDNA的获取为利用分子生物学方法对芋螺进行遗传进化分析和系统分类提供了基础。     

细胞程序性死亡与帕金森病的相关研究进展

帕金森病发病机制至今未明,近几年研究发现,线粒体依赖性PCD通路的激活在PD发病过程中是不可缺少的,不同形态学表现的细胞死亡形式在帕金森病发病过程中可以共同存在,而所有的这些细胞死亡都归因于PCD共同的上游通路的激活。PCD通路不仅仅是指线粒体介导的caspase依赖性凋亡,还包括非caspase依赖性细胞非凋亡性死亡,比如细胞坏死。这不仅仅是概念上的延伸,更为我们在帕金森病神经保护性治疗上提供了更多的靶点,有助于寻求神经保护的新方法和延缓神经退行性疾病的进程.抗凋亡治疗已经成为帕金森病等神经退行性疾病治疗的新热点,已经证实,caspase抑制剂能够通过抑制caspase的激活,阻止细胞退行性病变。那么将位于caspase执行者上游的Bax作为靶点,抑制Bax的激活与转位,能够产生更为持久显著的神经保护作用。本文综述了近年来相关研究进展。     

Hyperbaric oxygen induces apoptosis via a mitochondrial mechanism

During therapeutic hyperbaric oxygenation lymphocytes are exposed to high partial pressures of oxygen. This study aimed to analyze the mechanism of apoptosis induction by hyperbaric oxygen. For intervals of 0.5–4 h Jurkat-T-cells were exposed to ambient air or oxygen atmospheres at 1–3 absolute atmospheres. Apoptosis was analyzed by phosphatidylserine externalization, caspase-3 activation and DNA-fragmentation using flow cytometry. Apoptosis was already induced after 30 min of hyperbaric oxygenation (HBO, P < 0.05). The death receptor Fas was downregulated. Inhibition of caspase-9 but not caspase-8 blocked apoptosis induction by HBO. Hyperbaric oxygen caused a loss of mitochondrial membrane potential and caspase-9 induction. The mitochondrial pro-survival protein Bcl-2 was upregulated, and antagonizing Bcl-2 function potentiated apoptosis induction by HBO. In conclusion, a single exposure to hyperbaric oxygenation induces lymphocyte apoptosis by a mitochondrial and not a Fas-related mechanism. Regulation of Fas and Bcl-2 may be regarded as protective measures of the cell in response to hyperbaric oxygen.     

A characteristic pharmacological action of ‘Yang-invigorating’ Chinese tonifying herbs: Enhancement of myocardial ATP-generation capacity

In order to investigate the pharmacological basis of ‘Yang-invigorating’ action, the effect of oral treatment with the methanolic extract of ‘Yang-invigorating’ herbs on ATP-generation capacity was examined, using heart homogenates prepared from herb-pretreated mice. Tonifying (i.e., health-promoting) herbs of other functional categories were also included for comparison. The results indicated that ‘Yang-invigorating’ Chinese tonifying herbs could invariably enhance myocardial ATP-generation capacity, with the extent of stimulation varying among the herbs. In contrast, ‘Yin-nourishing’ herbs either did not stimulate or even decreased myocardial ATP-generation capacity. While ‘Qi-invigorating’ herbs produced variable effects on myocardial ATP-generation capacity, most of the ‘blood-enriching’ herbs did not cause any significant changes. The results obtained from studies using myocardial mitochondrial fractions isolated from herb-pretreated mice suggest that ‘Yang-invigorating’ herbs might speed up ATP generation by increasing mitochondrial electron transport. The ensemble of results has provided evidence for the first time to support the pharmacological basis of ‘Yang invigoration’ in Chinese medicine.     

Analysis of complete mitochondrial DNA sequences of three members of the Montastraea annularis coral species complex (Cnidaria, Anthozoa, Scleractinia)

Complete mitochondrial nucleotide sequences of two individuals each of Montastraea annularis, Montastraea faveolata, and Montastraea franksi were determined. Gene composition and order differed substantially from the sea anemone Metridium senile, but were identical to that of the phylogenetically distant coral genus Acropora. However, characteristics of the non-coding regions differed between the two scleractinian genera. Among members of the M. annularis complex, only 25 of 16,134 base pair positions were variable. Sixteen of these occurred in one colony of M. franksi, which (together with additional data) indicates the existence of multiple divergent mitochondrial lineages in this species. Overall, rates of evolution for these mitochondrial genomes were extremely slow (0.03–0.04% per million years based on the fossil record of the M. annularis complex). At higher taxonomic levels, patterns of genetic divergence and synonymous/nonsynonymous substitutions suggest non-neutral and unequal rates of evolution between the two lineages to which Montastraea and Acropora belong.     

Deficiency of the mitochondrial sulfide regulator ETHE1 disturbs cell growth,glutathione level and causes proteome alterations outside mitochondria

The mitochondrial enzyme ETHE1 is a persulfide dioxygenase essential for cellular sulfide detoxification, and its deficiency causes the severe and complex inherited metabolic disorder ethylmalonic encephalopathy (EE). In spite of well-described clinical symptoms of the disease, detailed cellular and molecular characterization is still ambiguous. Cellular redox regulation has been described to be influenced in ETHE1 deficient cells, and to clarify this further we applied image cytometry and detected decreased levels of reduced glutathione (GSH) in cultivated EE patient fibroblast cells. Cell growth initiation of the EE patient cells was impaired, whereas cell cycle regulation was not. Furthermore, Seahorse metabolic analyzes revealed decreased extracellular acidification, i. e. decreased lactate formation from glycolysis, in the EE patient cells. TMT-based large-scale proteomics was subsequently performed to broadly elucidate cellular consequences of the ETHE1 deficiency. More than 130 proteins were differentially regulated, of which the majority were non-mitochondrial. The proteomics data revealed a link between ETHE1-deficiency and down-regulation of several ribosomal proteins and LIM domain proteins important for cellular maintenance, and up-regulation of cell surface glycoproteins. Furthermore, several proteins of endoplasmic reticulum (ER) were perturbed including proteins influencing disulfide bond formation (e.g. protein disulfide isomerases and peroxiredoxin 4) and calcium-regulated proteins. The results indicate that decreased level of reduced GSH and alterations in proteins of ribosomes, ER and of cell adhesion lie behind the disrupted cell growth of the EE patient cells.     

基于线粒体12S rRNA和ND5基因序列的中国飞蝗属3亚种系统发育关系研究

对分布于中国的飞蝗Locusta migratoria Linnaeus 3亚种的线粒体12SrDNA(487bp)和ND5(451bp)基因的部分序列进行测定,与已知全线粒体基因组全序列的非洲飞蝗亚种进行序列比较,并在此基础上对ND5基因,以斑腿蝗科瘤喉蝗Parapodisma mikado为外群,重建MP树。基于序列长度的限制,将两基因联合分析重建了1棵最简约无根树。在对准的4个亚种共有的481bp的12SrDNA和451bp的ND5片断序列比较中,AT含量明显高于GC含量。由序列差异来看,哑洲飞蝗和东亚飞蝗序列相似度高,非洲飞蝗和西藏飞蝗相似度高,ND5基因的MP树和联合树也支持这个结论。由于大陆漂移和青藏高原隆起的特殊地质事件,正好解释了非洲飞蝗和西藏飞蝗的相似性,支持西藏飞蝗为单独1亚种,与非洲飞蝗为同一起源地,与其它2亚种相区别。     

Can we optimise the exercise training prescription to maximise improvements in mitochondria function and content?

Background

While there is agreement that exercise is a powerful stimulus to increase both mitochondrial function and content, we do not know the optimal training stimulus to maximise improvements in mitochondrial biogenesis.

Scope of review

This review will focus predominantly on the effects of exercise on mitochondrial function and content, as there is a greater volume of published research on these adaptations and stronger conclusions can be made.

Major conclusions

The results of cross-sectional studies, as well as training studies involving rats and humans, suggest that training intensity may be an important determinant of improvements in mitochondrial function (as determined by mitochondrial respiration), but not mitochondrial content (as assessed by citrate synthase activity). In contrast, it appears that training volume, rather than training intensity, may be an important determinant of exercise-induced improvements in mitochondrial content. Exercise-induced mitochondrial adaptations are quickly reversed following a reduction or cessation of physical activity, highlighting that skeletal muscle is a remarkably plastic tissue. Due to the small number of studies, more research is required to verify the trends highlighted in this review, and further studies are required to investigate the effects of different types of training on the mitochondrial sub-populations and also mitochondrial adaptations in different fibre types. Further research is also required to better understand how genetic variants influence the large individual variability for exercise-induced changes in mitochondrial biogenesis.

General significance

The importance of mitochondria for both athletic performance and health underlines the importance of better understanding the factors that regulate exercise-induced changes in mitochondrial biogenesis. This article is part of a Special Issue entitled Frontiers of Mitochondrial Research.