Dendritic mitochondria reach stable positions during circuit development

  1. Michelle C Faits
  2. Chunmeng Zhang
  3. Florentina Soto
  4. Daniel Kerschensteiner  Is a corresponding author
  1. Washington University School of Medicine, United States

Abstract

Mitochondria move throughout neuronal dendrites and localize to sites of energy demand. The prevailing view of dendritic mitochondria as highly motile organelles whose distribution is continually adjusted by neuronal activity via Ca2+-dependent arrests is based on observations in cultured neurons exposed to artificial stimuli. Here, we analyze the movements of mitochondria in ganglion cell dendrites in the intact retina. We find that whereas during development 30% of mitochondria are motile at any time, as dendrites mature, mitochondria all but stop moving and localize stably to synapses and branch points. Neither spontaneous nor sensory-evoked activity and Ca2+ transients alter motility of dendritic mitochondria; and pathological hyperactivity in a mouse model of retinal degeneration elevates rather than reduces motility. Thus, our findings indicate that dendritic mitochondria reach stable positions during a critical developmental period of high motility, and challenge current views about the role of activity in regulating mitochondrial transport in dendrites.

Article and author information

Author details

  1. Michelle C Faits

    Department of Ophthalmology and Visual Sciences, Washington University School of Medicine, Saint Louis, United States
    Competing interests
    The authors declare that no competing interests exist.
  2. Chunmeng Zhang

    Department of Ophthalmology and Visual Sciences, Washington University School of Medicine, St. Louis, United States
    Competing interests
    The authors declare that no competing interests exist.
  3. Florentina Soto

    Department of Ophthalmology and Visual Sciences, Washington University School of Medicine, St. Louis, United States
    Competing interests
    The authors declare that no competing interests exist.
  4. Daniel Kerschensteiner

    Department of Ophthalmology and Visual Sciences, Washington University School of Medicine, St. Louis, United States
    For correspondence
    dkerschensteiner@wustl.edu
    Competing interests
    The authors declare that no competing interests exist.

Reviewing Editor

  1. Richard J Youle, National Institute of Neurological Disorders and Stroke, National Institutes of Health, United States

Ethics

Animal experimentation: All animals were handled according to protocols approved by the Animal Studies Committee of Washington University School of Medicine (Protocol#: 20140095) and experiments were performed in compliance with the National Institutes of Health Guide for the Care and Use of Laboratory Animals.

Version history

  1. Received: September 14, 2015
  2. Accepted: December 30, 2015
  3. Accepted Manuscript published: January 7, 2016 (version 1)
  4. Version of Record published: January 28, 2016 (version 2)

Copyright

© 2016, Faits et al.

This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.

Metrics

  • 4,152
    views
  • 854
    downloads
  • 78
    citations

Views, downloads and citations are aggregated across all versions of this paper published by eLife.

Download links

A two-part list of links to download the article, or parts of the article, in various formats.

Downloads (link to download the article as PDF)

Open citations (links to open the citations from this article in various online reference manager services)

Cite this article (links to download the citations from this article in formats compatible with various reference manager tools)

  1. Michelle C Faits
  2. Chunmeng Zhang
  3. Florentina Soto
  4. Daniel Kerschensteiner
(2016)
Dendritic mitochondria reach stable positions during circuit development
eLife 5:e11583.
https://doi.org/10.7554/eLife.11583

Share this article

https://doi.org/10.7554/eLife.11583

Further reading

    1. Biochemistry and Chemical Biology
    2. Cell Biology
    Jiabin Pan, Rui Zhou ... Xiang-dong Li
    Research Article

    Transport and localization of melanosome at the periphery region of melanocyte are depended on myosin-5a (Myo5a), which associates with melanosome by interacting with its adaptor protein melanophilin (Mlph). Mlph contains four functional regions, including Rab27a-binding domain, Myo5a GTD-binding motif (GTBM), Myo5a exon F-binding domain (EFBD), and actin-binding domain (ABD). The association of Myo5a with Mlph is known to be mediated by two specific interactions: the interaction between the exon-F-encoded region of Myo5a and Mlph-EFBD and that between Myo5a-GTD and Mlph-GTBM. Here, we identify a third interaction between Myo5a and Mlph, that is, the interaction between the exon-G-encoded region of Myo5a and Mlph-ABD. The exon-G/ABD interaction is independent from the exon-F/EFBD interaction and is required for the association of Myo5a with melanosome. Moreover, we demonstrate that Mlph-ABD interacts with either the exon-G or actin filament, but cannot interact with both of them simultaneously. Based on above findings, we propose a new model for the Mlph-mediated Myo5a transportation of melanosomes.

    1. Cell Biology
    Yuhao Wang, Linhao Ruan ... Rong Li
    Research Article

    Mitochondria are the cellular energy hub and central target of metabolic regulation. Mitochondria also facilitate proteostasis through pathways such as the ‘mitochondria as guardian in cytosol’ (MAGIC) whereby cytosolic misfolded proteins (MPs) are imported into and degraded inside mitochondria. In this study, a genome-wide screen in Saccharomyces cerevisiae uncovered that Snf1, the yeast AMP-activated protein kinase (AMPK), inhibits the import of MPs into mitochondria while promoting mitochondrial biogenesis under glucose starvation. We show that this inhibition requires a downstream transcription factor regulating mitochondrial gene expression and is likely to be conferred through substrate competition and mitochondrial import channel selectivity. We further show that Snf1/AMPK activation protects mitochondrial fitness in yeast and human cells under stress induced by MPs such as those associated with neurodegenerative diseases.