1. Cell Biology
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Elimination of paternal mitochondria in mouse embryos occurs through autophagic degradation dependent on PARKIN and MUL1

  1. Rebecca Rojansky
  2. Moon-Yong Cha
  3. David C Chan  Is a corresponding author
  1. California Institute of Technology, United States
Research Article
  • Cited 133
  • Views 4,854
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Cite this article as: eLife 2016;5:e17896 doi: 10.7554/eLife.17896

Abstract

A defining feature of mitochondria is their maternal mode of inheritance. However, little is understood about the cellular mechanism through which paternal mitochondria, delivered from sperm, are eliminated from early mammalian embryos. Autophagy has been implicated in nematodes, but whether this mechanism is conserved in mammals has been disputed. Here we show that cultured mouse fibroblasts and pre-implantation embryos use a common pathway for elimination of mitochondria. Both situations utilize mitophagy, in which mitochondria are sequestered by autophagosomes and delivered to lysosomes for degradation. The E3 ubiquitin ligases PARKIN and MUL1 play redundant roles in elimination of paternal mitochondria. The process is associated with depolarization of paternal mitochondria and additionally requires the mitochondrial outer membrane protein FIS1, the autophagy adaptor P62, and PINK1 kinase. Our results indicate that strict maternal transmission of mitochondria relies on mitophagy and uncover a collaboration between MUL1 and PARKIN in this process.

Article and author information

Author details

  1. Rebecca Rojansky

    Division of Biology and Biological Engineering, California Institute of Technology, Pasadena, United States
    Competing interests
    The authors declare that no competing interests exist.
  2. Moon-Yong Cha

    Division of Biology and Biological Engineering, California Institute of Technology, Pasadena, United States
    Competing interests
    The authors declare that no competing interests exist.
  3. David C Chan

    Division of Biology and Biological Engineering, California Institute of Technology, Pasadena, United States
    For correspondence
    dchan@caltech.edu
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-0191-2154

Funding

National Institutes of Health (GM119388)

  • David C Chan

National Institutes of Health (GM083121)

  • David C Chan

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

Reviewing Editor

  1. Serge Przedborski, Columbia University Medical Center, United States

Publication history

  1. Received: May 17, 2016
  2. Accepted: November 14, 2016
  3. Accepted Manuscript published: November 17, 2016 (version 1)
  4. Version of Record published: November 29, 2016 (version 2)

Copyright

© 2016, Rojansky 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.

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