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      Trans-mitochondrial coordination of cristae at regulated membrane junctions

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          Abstract

          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.

          Abstract

          Mammalian mitochondria are capable of inter-organelle communication, but connections between mitochondria have not been defined. Here, Picard et al. report the presence of inter-mitochondrial junctions, electron-dense regions with coordinated inner membrane cristae that do not depend on mitofusins for their formation.

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          Automated electron microscope tomography using robust prediction of specimen movements.

          A new method was developed to acquire images automatically at a series of specimen tilts, as required for tomographic reconstruction. The method uses changes in specimen position at previous tilt angles to predict the position at the current tilt angle. Actual measurement of the position or focus is skipped if the statistical error of the prediction is low enough. This method allows a tilt series to be acquired rapidly when conditions are good but falls back toward the traditional approach of taking focusing and tracking images when necessary. The method has been implemented in a program, SerialEM, that provides an efficient environment for data acquisition. This program includes control of an energy filter as well as a low-dose imaging mode, in which tracking and focusing occur away from the area of interest. The program can automatically acquire a montage of overlapping frames, allowing tomography of areas larger than the field of the CCD camera. It also includes tools for navigating between specimen positions and finding regions of interest.
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            Computer visualization of three-dimensional image data using IMOD.

            We have developed a computer software package, IMOD, as a tool for analyzing and viewing three-dimensional biological image data. IMOD is useful for studying and modeling data from tomographic, serial section, and optical section reconstructions. The software allows image data to be visualized by several different methods. Models of the image data can be visualized by volume or contour surface rendering and can yield quantitative information.
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              Bacterial quorum-sensing network architectures.

              Quorum sensing is a cell-cell communication process in which bacteria use the production and detection of extracellular chemicals called autoinducers to monitor cell population density. Quorum sensing allows bacteria to synchronize the gene expression of the group, and thus act in unison. Here, we review the mechanisms involved in quorum sensing with a focus on the Vibrio harveyi and Vibrio cholerae quorum-sensing systems. We discuss the differences between these two quorum-sensing systems and the differences between them and other paradigmatic bacterial signal transduction systems. We argue that the Vibrio quorum-sensing systems are optimally designed to precisely translate extracellular autoinducer information into internal changes in gene expression. We describe how studies of the V. harveyi and V. cholerae quorum-sensing systems have revealed some of the fundamental mechanisms underpinning the evolution of collective behaviors.
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                Author and article information

                Journal
                Nat Commun
                Nat Commun
                Nature Communications
                Nature Pub. Group
                2041-1723
                17 February 2015
                : 6
                : 6259
                Affiliations
                [1 ]Center for Mitochondrial and Epigenomic Medicine, The Children’s Hospital of Philadelphia and University of Pennsylvania , Philadelphia, Pennsylvania 19104, USA
                [2 ]MitoCare Center, Department of Pathology, Anatomy and Cell Biology, Thomas Jefferson University , Philadelphia, Pennsylvania 19107, USA
                [3 ]Department of Physiology, Semmelweis University , P.O. Box 259, Budapest H-1444, Hungary
                [4 ]Center for Pharmacogenomics, Department of Internal Medicine, Washington University School of Medicine , St Louis, Missouri 63110, USA
                [5 ]Penn EM Resource Laboratory, University of Pennsylvania , Philadelphia, Pennsylvania 19104, USA
                Author notes
                Article
                ncomms7259
                10.1038/ncomms7259
                4332397
                25687472
                693df98a-db6b-4bf8-961e-e9098df71ac1
                Copyright © 2015, Nature Publishing Group, a division of Macmillan Publishers Limited. All Rights Reserved.

                This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/

                History
                : 30 September 2014
                : 09 January 2015
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