Regulation of mitochondria-dynactin interaction and mitochondrial retrograde transport in axons

  1. Catherine M Drerup  Is a corresponding author
  2. Amy L Herbert
  3. Kelly R Monk
  4. Alex V Nechiporuk  Is a corresponding author
  1. Oregon Health and Science University, United States
  2. Washington University School of Medicine, United States

Abstract

Mitochondrial transport in axons is critical for neural circuit health and function. While several proteins have been found that modulate bidirectional mitochondrial motility, factors that regulate unidirectional mitochondrial transport have been harder to identify. In a genetic screen, we found a zebrafish strain in which mitochondria fail to attach to the dynein retrograde motor. This strain carries a loss-of-function mutation in actr10, a member of the dynein-associated complex dynactin. The abnormal axon morphology and mitochondrial retrograde transport defects observed in actr10 mutants are distinct from dynein and dynactin mutant axonal phenotypes. In addition, Actr10 lacking the dynactin binding domain maintains its ability to bind mitochondria, arguing for a role for Actr10 in dynactin-mitochondria interaction. Finally, genetic interaction studies implicated Drp1 as a partner in Actr10-dependent mitochondrial retrograde transport. Together, this work identifies Actr10 as a factor necessary for dynactin-mitochondria interaction, enhancing our understanding of how mitochondria properly localize in axons.

Article and author information

Author details

  1. Catherine M Drerup

    Department of Cell, Developmental and Cancer Biology, Oregon Health and Science University, Portland, United States
    For correspondence
    katie.drerup@nih.gov
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-0219-3075
  2. Amy L Herbert

    Department of Developmental Biology, Washington University School of Medicine, St. Louis, United States
    Competing interests
    The authors declare that no competing interests exist.
  3. Kelly R Monk

    Department of Developmental Biology, Washington University School of Medicine, St. Louis, United States
    Competing interests
    The authors declare that no competing interests exist.
  4. Alex V Nechiporuk

    Department of Cell, Developmental and Cancer Biology, Oregon Health and Science University, Portland, United States
    For correspondence
    nechipor@ohsu.edu
    Competing interests
    The authors declare that no competing interests exist.

Funding

National Institute of Neurological Disorders and Stroke (1K99NS086903)

  • Catherine M Drerup

Eunice Kennedy Shriver National Institute of Child Health and Human Development (R01HD072844)

  • Alex V Nechiporuk

OHSU Center for Spatial Systems Biomedicine (GBMEN0245A1)

  • Alex V Nechiporuk

National Institute of Neurological Disorders and Stroke (F31 NS096814)

  • Amy L Herbert

Philip and Seema Needleman (Graduate Student Fellowship)

  • Amy L Herbert

National Multiple Sclerosis Society (Harry Weaver Scholar)

  • Kelly R Monk

The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.

Ethics

Animal experimentation: This study was performed in strict accordance with the recommendations specified in the Oregon Health and Science University Guide for the Care and Use of Laboratory Animals. All animals were handled in accordance with the institutional animal care and use committee (IACUC) protocol # IS00002972.

Reviewing Editor

  1. Tanya T Whitfield, University of Sheffield, United Kingdom

Publication history

  1. Received: October 9, 2016
  2. Accepted: April 12, 2017
  3. Accepted Manuscript published: April 17, 2017 (version 1)
  4. Version of Record published: May 2, 2017 (version 2)

Copyright

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.

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  1. Catherine M Drerup
  2. Amy L Herbert
  3. Kelly R Monk
  4. Alex V Nechiporuk
(2017)
Regulation of mitochondria-dynactin interaction and mitochondrial retrograde transport in axons
eLife 6:e22234.
https://doi.org/10.7554/eLife.22234
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