5
views
0
recommends
+1 Recommend
0 collections
    0
    shares
      • Record: found
      • Abstract: found
      • Article: found
      Is Open Access

      Synaptic mitochondria regulate hair-cell synapse size and function

      research-article

      Read this article at

      Bookmark
          There is no author summary for this article yet. Authors can add summaries to their articles on ScienceOpen to make them more accessible to a non-specialist audience.

          Abstract

          Sensory hair cells in the ear utilize specialized ribbon synapses. These synapses are defined by electron-dense presynaptic structures called ribbons, composed primarily of the structural protein Ribeye. Previous work has shown that voltage-gated influx of Ca 2+ through Ca V1.3 channels is critical for hair-cell synapse function and can impede ribbon formation. We show that in mature zebrafish hair cells, evoked presynaptic-Ca 2+ influx through Ca V1.3 channels initiates mitochondrial-Ca 2+ (mito-Ca 2+) uptake adjacent to ribbons. Block of mito-Ca 2+ uptake in mature cells depresses presynaptic-Ca 2+ influx and impacts synapse integrity. In developing zebrafish hair cells, mito-Ca 2+ uptake coincides with spontaneous rises in presynaptic-Ca 2+ influx. Spontaneous mito-Ca 2+ loading lowers cellular NAD +/NADH redox and downregulates ribbon size. Direct application of NAD + or NADH increases or decreases ribbon size respectively, possibly acting through the NAD(H)-binding domain on Ribeye. Our results present a mechanism where presynaptic- and mito-Ca 2+ couple to confer proper presynaptic function and formation.

          eLife digest

          Hearing depends upon specialized cells deep within the ear called hair cells. These cells take their name from the bundles of hair-like fibers found on their surface, which move when sound waves enter the ear. This movement activates the hair cells, which send signals to nearby neurons at contact points called synapses. Hair cells must send messages to their synaptic partners rapidly and continuously in order for humans to follow complex streams of sound, such as speech. This requires large amounts of energy, which are produced by compartments inside the hair cells called mitochondria.

          Wong et al. show that mitochondria, which are often described as the ‘power plants’ of cells, are critical for hair cell synapses to form and work correctly. But rather than studying hair cells in the human ear, Wong et al. took advantage of the fact that another species – the zebrafish – has hair cells on its body surface. These cells detect movements in water rather than sound waves, but they work in much the same way as hair cells in the ear, and are easier to access and study.

          Wong et al. report that in zebrafish larvae, developing hair cells send spontaneous signals to their contact neurons even before they start receiving any sensory input. But if mitochondria in the hair cells fail to detect these signals, the synapses fail to form correctly. In older zebrafish, mature hair cells send signals to their synaptic partners whenever they detect sensory input. But if mitochondria fail to detect these signals, the synapses stop working and ultimately break down.

          These findings help explain why damage to mitochondria in the inner ear can lead to hearing loss. Moreover, because mitochondria are present in almost all cells, their disruption causes a wide range of diseases. Many of these involve the brain, which requires large amounts of energy and so is particularly vulnerable to mitochondrial damage. These results may provide insights into such disorders.

          Related collections

          Most cited references105

          • Record: found
          • Abstract: found
          • Article: not found

          The Tol2kit: a multisite gateway-based construction kit for Tol2 transposon transgenesis constructs.

          Transgenesis is an important tool for assessing gene function. In zebrafish, transgenesis has suffered from three problems: the labor of building complex expression constructs using conventional subcloning; low transgenesis efficiency, leading to mosaicism in transient transgenics and infrequent germline incorporation; and difficulty in identifying germline integrations unless using a fluorescent marker transgene. The Tol2kit system uses site-specific recombination-based cloning (multisite Gateway technology) to allow quick, modular assembly of [promoter]-[coding sequence]-[3' tag] constructs in a Tol2 transposon backbone. It includes a destination vector with a cmlc2:EGFP (enhanced green fluorescent protein) transgenesis marker and a variety of widely useful entry clones, including hsp70 and beta-actin promoters; cytoplasmic, nuclear, and membrane-localized fluorescent proteins; and internal ribosome entry sequence-driven EGFP cassettes for bicistronic expression. The Tol2kit greatly facilitates zebrafish transgenesis, simplifies the sharing of clones, and enables large-scale projects testing the functions of libraries of regulatory or coding sequences. Copyright 2007 Wiley-Liss, Inc.
            Bookmark
            • Record: found
            • Abstract: found
            • Article: not found

            Mitochondrial transport in neurons: impact on synaptic homeostasis and neurodegeneration.

            Mitochondria have a number of essential roles in neuronal function. Their complex mobility patterns within neurons are characterized by frequent changes in direction. Mobile mitochondria can become stationary or pause in regions that have a high metabolic demand and can move again rapidly in response to physiological changes. Defects in mitochondrial transport are implicated in the pathogenesis of several major neurological disorders. Research into the mechanisms that regulate mitochondrial transport is thus an important emerging frontier.
              Bookmark
              • Record: found
              • Abstract: found
              • Article: found
              Is Open Access

              TANGO: a generic tool for high-throughput 3D image analysis for studying nuclear organization

              Motivation: The cell nucleus is a highly organized cellular organelle that contains the genetic material. The study of nuclear architecture has become an important field of cellular biology. Extracting quantitative data from 3D fluorescence imaging helps understand the functions of different nuclear compartments. However, such approaches are limited by the requirement for processing and analyzing large sets of images. Results: Here, we describe Tools for Analysis of Nuclear Genome Organization (TANGO), an image analysis tool dedicated to the study of nuclear architecture. TANGO is a coherent framework allowing biologists to perform the complete analysis process of 3D fluorescence images by combining two environments: ImageJ (http://imagej.nih.gov/ij/) for image processing and quantitative analysis and R (http://cran.r-project.org) for statistical processing of measurement results. It includes an intuitive user interface providing the means to precisely build a segmentation procedure and set-up analyses, without possessing programming skills. TANGO is a versatile tool able to process large sets of images, allowing quantitative study of nuclear organization. Availability: TANGO is composed of two programs: (i) an ImageJ plug-in and (ii) a package (rtango) for R. They are both free and open source, available (http://biophysique.mnhn.fr/tango) for Linux, Microsoft Windows and Macintosh OSX. Distribution is under the GPL v.2 licence. Contact: thomas.boudier@snv.jussieu.fr Supplementary information: Supplementary data are available at Bioinformatics online.
                Bookmark

                Author and article information

                Contributors
                Role: Reviewing Editor
                Role: Senior Editor
                Journal
                eLife
                Elife
                eLife
                eLife
                eLife Sciences Publications, Ltd
                2050-084X
                14 October 2019
                2019
                : 8
                : e48914
                Affiliations
                [1 ]deptSection on Sensory Cell Development and Function National Institute on Deafness and Other Communication Disorders, National Institutes of Health BethesdaUnited States
                [2 ]deptNational Institutes of Health-Johns Hopkins University Graduate Partnership Program National Institute on Deafness and Other Communication Disorders, National Institutes of Health BethesdaUnited States
                [3 ]deptAdvanced Imaging Core National Institute on Deafness and Other Communication Disorders, National Institutes of Health BethesdaUnited States
                University of Sheffield United Kingdom
                University of Oxford United Kingdom
                University of Sheffield United Kingdom
                Helmholtz Zentrum München Germany
                University of Illinois United States
                Author information
                https://orcid.org/0000-0001-5826-8526
                https://orcid.org/0000-0002-1065-8215
                Article
                48914
                10.7554/eLife.48914
                6879205
                31609202
                42544cdb-270f-4d52-9a2c-4b5d293fd633

                This is an open-access article, free of all copyright, and may be freely reproduced, distributed, transmitted, modified, built upon, or otherwise used by anyone for any lawful purpose. The work is made available under the Creative Commons CC0 public domain dedication.

                History
                : 30 May 2019
                : 13 October 2019
                Funding
                Funded by: FundRef http://dx.doi.org/10.13039/100000055, National Institute on Deafness and Other Communication Disorders;
                Award ID: 1ZIADC000085-01
                Award Recipient :
                Funded by: FundRef http://dx.doi.org/10.13039/100000055, National Institute on Deafness and Other Communication Disorders;
                Award ID: ZICDC000081
                Award Recipient :
                The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
                Categories
                Research Article
                Developmental Biology
                Neuroscience
                Custom metadata
                Mitochondrial calcium influx plays distinct roles in presynapse formation, function and stability in sensory hair cells.

                Life sciences
                mitochondrial calcium,ribbon synapse,metabolism,sensory cell,zebrafish
                Life sciences
                mitochondrial calcium, ribbon synapse, metabolism, sensory cell, zebrafish

                Comments

                Comment on this article