Cardiac mitochondrial ATP-sensitive potassium channel is activated by nitric oxide in vitro

Previous observations on the activation of the mitochondrial ATP-sensitive potassium channel (mitoK(ATP)) by nitric oxide (NO) in myocardial preconditioning were based on indirect evidence. In this study, we have investigated the direct effect of NO on the rat cardiac mitoK(ATP) after reconstitution of the inner mitochondrial membranes into lipid bilayers. We found that the mitoK(ATP) was activated by exogenous NO donor S-nitroso-N-acetyl penicillamine or PAPA NONOate. This activation was inhibited by mitoK(ATP) blockers 5-hydroxydecanoate or glibenclamide. Our observations confirm that NO can directly activate the cardiac mitoK(ATP), which may underlie its contribution to myocardial preconditioning.     

Mitochondrial unfolded protein response gene Clpp is required to maintain ovarian follicular reserve during aging,for oocyte competence,and development of pre‐implantation embryos

Caseinolytic peptidase P mediates degradation of unfolded mitochondrial proteins and activates mitochondrial unfolded protein response (mtUPR) to maintain protein homeostasis. Clpp^?/? female mice generate a lower number of mature oocytes and two‐cell embryos, and no blastocysts. Clpp^?/? oocytes have smaller mitochondria, with lower aspect ratio (length/width), and decreased expression of genes that promote fusion. A 4‐fold increase in atretic follicles at 3 months, and reduced number of primordial follicles at 6–12 months are observed in Clpp^?/? ovaries. This is associated with upregulation of p‐S6, p‐S6K, p‐4EBP1 and p‐AKT473, p‐mTOR2481 consistent with mTORC1 and mTORC2 activation, respectively, and Clpp^?/? oocyte competence is partially rescued by mTOR inhibitor rapamycin. Our findings demonstrate that CLPP is required for oocyte and embryo development and oocyte mitochondrial function and dynamics. Absence of CLPP results in mTOR pathway activation, and accelerated depletion of ovarian follicular reserve.     

Focus: The Science of Stress: Oxidative Stress and Inflammation in Cardiovascular Diseases and Cancer: Role of Non-coding RNAs

High oxidative stress, Th1/Th17 immune response, M1 macrophage inflammation, and cell death are associated with cardiovascular diseases. Controlled oxidative stress, Th2/Treg anti-tumor immune response, M2 macrophage inflammation, and survival are associated with cancer. MiR-21 protects against cardiovascular diseases but may induce tumor growth by retaining the anti-inflammatory M2 macrophage and Treg phenotypes and inhibiting apoptosis. Down-regulation of let-7, miR-1, miR-9, miR-16, miR-20a, miR-22a, miR-23a, miR-24a, miR-26a, miR-29, miR-30a, miR-34a, miR-124, miR-128, miR-130a, miR-133, miR-140, miR-143-145, miR-150, miR-153, miR-181a, miR-378, and miR-383 may aid cancer cells to escape from stresses. Upregulation of miR-146 and miR-223 may reduce anti-tumor immune response together with miR-21 that also protects against apoptosis. MiR-155 and silencing of let-7e, miR-125, and miR-126 increase anti-tumor immune response. MiR expression depends on oxidative stress, cytokines, MYC, and TGF-β, and expression of silencing lncRNAs and circ-RNAs. However, one lncRNA or circ-RNA may have opposite effects by targeting several miRs. For example, PVT1 induces apoptosis by targeting miR-16a and miR-30a but inhibits apoptosis by silencing miR-17. In addition, levels of a non-coding RNA in a cell type depend not only on expression in that cell type but also on an exchange of microvesicles between cell types and tumors. Although we got more insight into the function of a growing number of individual non-coding RNAs, overall, we do not know enough how several of them interact in functional networks and how their expression changes at different stages of disease progression.     

LOCAL CYTONUCLEAR EXTINCTION OF THE GOLDEN-WINGED WARBLER

I compared the mtDNA compositions of two adjacent populations of Vermivora chrysoptera (golden-winged warbler) at different stages of transient hybridization with its sister species V. pinus (blue-winged warbler). Pinus mtDNA introgresses asymmetrically and perhaps rapidly into chrysoptera phenotypes without comparable reverse introgression of chrysoptera mtDNA into replacing pinus populations. Pinus mtDNA was virtually fixed (98%) in an actively hybridizing lowland population with varied phenotypes. Pinus mtDNA increased from 27% (n = 11) in 1988 to 70% (n = 10) in 1992 in successive samples of a highland population in the initial stages of hybridization. This population comprised mostly pure and slightly introgressed chrysoptera phenotypes. The rapid pace of asymmetrical introgression may be the result of initial invasion of chrysoptera populations by pioneering female pinus and/or an unknown competitive advantage of pinus females and their daughters over chrysoptera females.     

Genetic population structure of the net-winged midge, Elporia barnardi (Diptera: Blephariceridae) in streams of the south-western Cape, South Africa: implications for dispersal

SUMMARY 1. The net‐winged midges (Diptera: Blephariceridae), with highly specific habitat requirements and specialised morphological adaptations, exhibit high habitat fidelity and a limited potential for dispersal. Given the longitudinal and hierarchical nature of lotic systems, along with the geological structure of catchment units, we hypothesise that populations of net‐winged midge should exhibit a high degree of population sub‐structuring. 2. Sequence variation in the cytochrome c oxidase subunit I (COI) region of the mitochondrial DNA (mtDNA) was examined to determine patterns of genetic variation and infer historical and contemporary processes important in the genetic structuring of populations of Elporia barnardi. The DNA variation was examined at sites within streams, between streams in the same range, and between mountain ranges in the south‐western Cape of South Africa. 3. Twenty‐five haplotypes, 641 bp in length, were identified from the 93 individuals sampled. A neighbour‐joining tree revealed two highly divergent clades (～5%) corresponding to populations from the two mountain ranges. A number of monophyletic groups were identified within each clade, associated with individual catchment units. 4. The distribution of genetic variation was examined using analysis of molecular variance (amova ). This showed most of the variation to be distributed among the two ranges (～80%), with a small percentage (～15%) distributed among streams within each range. Similarly, variation among streams on Table Mountain was primarily distributed among catchment units (86%). A Mantel's test revealed a significant relationship between genetic differentiation and geographical distance, suggesting isolation by distance (P < 0.001). 5. Levels of sequence divergence between the two major clades, representing the two mountain ranges, are comparable with those of some intra‐generic species comparisons. Vicariant events, such as the isolation of the Peninsula mountain chain and Table Mountain, may have been important in the evolution of what is now a highly endemic fauna. 6. The monophyletic nature of the catchment units suggests that dispersal is confined to the stream environment and that mountain ridges provide effective physical barriers to dispersal of E. barnardi.     

Decreased mitochondrial OGG1 expression is linked to mitochondrial defects and delayed hepatoma cell growth

Many solid tumor cells exhibit mitochondrial respiratory impairment; however, the mechanisms of such impairment in cancer development remain unclear. Here, we demonstrate that SNU human hepatoma cells with declined mitochondrial respiratory activity showed decreased expression of mitochondrial 8-oxoguanine DNA glycosylase/lyase (mtOGG1), a mitochondrial DNA repair enzyme; similar results were obtained with human hepatocellular carcinoma tissues. Among several OGG1-2 variants with a mitochondrial-targeting sequence (OGG1-2a, -2b, -2c, -2d, and -2e), OGG1-2a was the major mitochondrial isoform in all examined hepatoma cells. Interestingly, hepatoma cells with low mtOGG1 levels showed delayed cell growth and increased intracellular reactive oxygen species (ROS) levels. Knockdown of OGG1-2 isoforms in Chang-L cells, which have active mitochondrial respiration with high mtOGG1 levels, significantly decreased cellular respiration and cell growth, and increased intracellular ROS. Overexpression of OGG1-2a in SNU423 cells, which have low mtOGG1 levels, effectively recovered cellular respiration and cell growth activities, and decreased intracellular ROS. Taken together, our results suggest that mtOGG1 plays an important role in maintaining mitochondrial respiration, thereby contributing to cell growth of hepatoma cells.     

Dysfunction of rat liver mitochondria by selenite: induction of mitochondrial permeability transition through thiol-oxidation

Selenium is an essential trace element in mammals and is thought to play a chemopreventive role in human cancer, possibly by inducing tumor cell apoptosis. Mitochondria play a pivotal role in the induction of apoptosis in many cell types. The effects of selenite on mitochondrial function were therefore investigated. Selenite induced the oxidation and cross-linking of protein thiol groups, mitochondrial permeability transition (MPT), a decrease in the mitochondrial membrane potential, and the release of cytochrome c in mitochondria isolated from rat liver. Induction of the MPT by selenite was prevented by cyclosporin A, EGTA, or N-ethylmaleimide. These results thus indicate that selenite induces the MPT as a result of direct modification of protein thiol groups, resulting in the release of cytochrome c and a loss of mitochondrial membrane potential.     

Phylogeography of a northeast Asian spruce, Picea jezoensis, inferred from genetic variation observed in organelle DNA markers

Range-wide genetic variation of the widespread cold-temperate spruce Picea jezoensis was studied throughout northeast Asia using maternally inherited mitochondrial DNA and paternally inherited chloroplast DNA markers. This study assessed 33 natural populations including three varieties of the species in Japan, Russia, China, and South Korea. We depicted sharp suture zones in straits around Japan in the geographical distribution pattern of mitochondrial haplotypes (GST=0.901; NST=0.934). In contrast, we detected possible extensive pollen flow without seed flow across the straits around Japan during the past population history in the distribution pattern of chloroplast haplotypes (GST=0.233; NST=0.333). The analysis of isolation by distance of the species implied that by acting as a barrier for the movement of seeds and pollen, the sharp suture zones contributed considerably to the level of genetic differentiation between populations. Constructed networks of mitochondrial haplotypes allowed inference of the phylogeographical history of the species. We deduced that the disjunction with Kamchatka populations reflects range expansion and contraction to the north of the current distribution. Within Japan, we detected phylogeographically different types of P. jezoensis between Hokkaido and Honshu islands; P. jezoensis in Honshu Island may have colonized this region from the Asian continent via the Korean peninsula and the species in Hokkaido Island is likely to have spread from the Asian continent via Sakhalin through land bridges. Japanese endemism of mitochondrial haplotypes in Hokkaido and Honshu islands might have been promoted by separation of these islands from each other and from the Asian continent by the straits during the late Quaternary.