25 research outputs found

    Trans-mitochondrial coordination of cristae at regulated membrane junctions

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    Reminiscent of bacterial quorum sensing, mammalian mitochondria participate in inter-organelle communication. However, physical structures that enhance or enable interactions between mitochondria have not been defined. Here we report that adjacent mitochondria exhibit coordination of inner mitochondrial membrane cristae at inter-mitochondrial junctions (IMJs). These electron-dense structures are conserved across species, resistant to genetic disruption of cristae organization, dynamically modulated by mitochondrial bioenergetics, independent of known inter-mitochondrial tethering proteins mitofusins and rapidly induced by the stable rapprochement of organelles via inducible synthetic linker technology. At the associated junctions, the cristae of adjacent mitochondria form parallel arrays perpendicular to the IMJ, consistent with a role in electrochemical coupling. These IMJs and associated cristae arrays may provide the structural basis to enhance the propagation of intracellular bioenergetic and apoptotic waves through mitochondrial networks within cells

    Evaluation of Microorganisms Cultured from Injured and Repressed Tissue Regeneration Sites in Endangered Giant Aquatic Ozark Hellbender Salamanders

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    Investigation into the causes underlying the rapid, global amphibian decline provides critical insight into the effects of changing ecosystems. Hypothesized and confirmed links between amphibian declines, disease, and environmental changes are increasingly represented in published literature. However, there are few long-term amphibian studies that include data on population size, abnormality/injury rates, disease, and habitat variables to adequately assess changes through time. We cultured and identified microorganisms isolated from abnormal/injured and repressed tissue regeneration sites of the endangered Ozark Hellbender, Cryptobranchus alleganiensis bishopi, to discover potential causative agents responsible for their significant decline in health and population. This organism and our study site were chosen because the population and habitat of C. a. bishopi have been intensively studied from 1969–2009, and the abnormality/injury rate and apparent lack of regeneration were established. Although many bacterial and fungal isolates recovered were common environmental organisms, several opportunistic pathogens were identified in association with only the injured tissues of C.a. bishopi. Bacterial isolates included Aeromonas hydrophila, a known amphibian pathogen, Granulicetella adiacens, Gordonai terrae, Stenotrophomonas maltophilia, Aerococcus viridans, Streptococcus pneumoniae and a variety of Pseudomonads, including Pseudomonas aeruginosa, P. stutzeri, and P. alcaligenes. Fungal isolates included species in the genera Penicillium, Acremonium, Cladosporium, Curvularia, Fusarium, Streptomycetes, and the Class Hyphomycetes. Many of the opportunistic pathogens identified are known to form biofilms. Lack of isolation of the same organism from all wounds suggests that the etiological agent responsible for the damage to C. a. bishopi may not be a single organism. To our knowledge, this is the first study to profile the external microbial consortia cultured from a Cryptobranchid salamander. The incidence of abnormalities/injury and retarded regeneration in C. a. bishopi may have many contributing factors including disease and habitat degradation. Results from this study may provide insight into other amphibian population declines

    The role of the mitochondria and the endoplasmic reticulum contact sites in the development of the immune responses

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    Abstract Mitochondria and endoplasmic reticulum (ER) contact sites (MERCs) are dynamic modules enriched in subset of lipids and specialized proteins that determine their structure and functions. The MERCs regulate lipid transfer, autophagosome formation, mitochondrial fission, Ca2+ homeostasis and apoptosis. Since these functions are essential for cell biology, it is therefore not surprising that MERCs also play a critical role in organ physiology among which the immune system stands by its critical host defense function. This defense system must discriminate and tolerate host cells and beneficial commensal microorganisms while eliminating pathogenic ones in order to preserve normal homeostasis. To meet this goal, the immune system has two lines of defense. First, the fast acting but unspecific innate immune system relies on anatomical physical barriers and subsets of hematopoietically derived cells expressing germline-encoded receptors called pattern recognition receptors (PRR) recognizing conserved motifs on the pathogens. Second, the slower but very specific adaptive immune response is added to complement innate immunity. Adaptive immunity relies on another set of specialized cells, the lymphocytes, harboring receptors requiring somatic recombination to be expressed. Both innate and adaptive immune cells must be activated to phagocytose and process pathogens, migrate, proliferate, release soluble factors and destroy infected cells. Some of these functions are strongly dependent on lipid transfer, autophagosome formation, mitochondrial fission, and Ca2+ flux; this indicates that MERCs could regulate immunity

    Fur seals at Macquarie Island: post-sealing colonisation, trends in abundance and hybridisation of three species

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    © Springer-Verlag 2009Commercial sealers exterminated the original fur seal population at Macquarie Island in the early 1800s. The first breeding record since the sealing era was not reported until March 1955. Three species of fur seal now occur at Macquarie Island, the Antarctic (Arctocephalus gazella), subantarctic (A. tropicalis) and New Zealand (A. forsteri) fur seal. Census data from 54 breeding seasons in the period 1954–2007 were used to estimate population status and growth for each species. Between the 1950s and 1970s, annual increases in pup production for the species aggregate were low. Between 1986 and 2007, pup production of Antarctic fur seals increased by about 8.8% per year and subantarctic fur seals by 6.8% per year. The New Zealand fur seal, although the most numerous fur seal species on Macquarie Island, has yet to establish a breeding population, due to the absence of reproductively mature females. Hybridisation among species is significant, but appears to be declining. The slow establishment and growth of fur seal populations on Macquarie Island appears to have been affected by its distance from major population centres and hence low immigration rates, asynchronous colonisation times of males and females of each species, and extensive hybridisation.Simon David Goldsworthy, Jane McKenzie, Brad Page, Melanie L. Lancaster, Peter D. Shaughnessy, Louise P. Wynen, Susan A. Robinson, Kristian J. Peters, Alastair M. M. Baylis and Rebecca R. McIntos

    MICU3 is a tissue-specific enhancer of mitochondrial calcium uptake

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    The versatility and universality of Ca2+ as intracellular messenger is guaranteed by the compartmentalization of changes in [Ca2+]. In this context, mitochondrial Ca2+ plays a central role, by regulating both specific organelle functions and global cellular events. This versatility is also guaranteed by a cell type-specific Ca2+ signaling toolkit controlling specific cellular functions. Accordingly, mitochondrial Ca2+ uptake is mediated by a multimolecular structure, the MCU complex, which differs among various tissues. Its activity is indeed controlled by different components that cooperate to modulate specific channeling properties. We here investigate the role of MICU3, an EF-hand containing protein expressed at high levels, especially in brain. We show that MICU3 forms a disulfide bond-mediated dimer with MICU1, but not with MICU2, and it acts as enhancer of MCU-dependent mitochondrial Ca2+ uptake. Silencing of MICU3 in primary cortical neurons impairs Ca2+ signals elicited by synaptic activity, thus suggesting a specific role in regulating neuronal function
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