Electron transport chain biogenesis activated by a JNK-insulin-Myc relay primes mitochondrial inheritance in Drosophila

  1. Zong-Heng Wang
  2. Yi Liu
  3. Vijender Chaitankar
  4. Mehdi Pirooznia
  5. Hong Xu  Is a corresponding author
  1. National Heart, Lung, and Blood Institute, National Institutes of Health, United States

Abstract

Oogenesis features an enormous increase in mitochondrial mass and mtDNA copy number, which are required to furnish mature eggs with an adequate supply of mitochondria and to curb the transmission of deleterious mtDNA variants. Quiescent in dividing germ cells, mtDNA replication initiates upon oocyte determination in the Drosophila ovary, which necessitates active mitochondrial respiration. However, the underlying mechanism for this dynamic regulation remains unclear. Here, we show that an feedforward insulin-Myc loop promotes mitochondrial respiration and biogenesis by boosting the expression of electron transport chain subunits and of factors essential for mtDNA replication and expression, and for the import of mitochondrial proteins. We further reveal that transient activation of JNK enhances the expression of the insulin receptor and initiates the insulin-Myc signaling loop. This signaling relay promotes mitochondrial biogenesis in the ovary, and thereby plays a role in limiting the transmission of deleterious mtDNA mutations. Our study demonstrates cellular mechanisms that couple mitochondrial biogenesis and inheritance with oocyte development.

Data availability

The data were deposited in Gene Expression Omnibus of NCBI and will be available with accession number (GEO: GSE126997).

The following data sets were generated
The following previously published data sets were used

Article and author information

Author details

  1. Zong-Heng Wang

    National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, United States
    Competing interests
    The authors declare that no competing interests exist.
  2. Yi Liu

    National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, United States
    Competing interests
    The authors declare that no competing interests exist.
  3. Vijender Chaitankar

    National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, United States
    Competing interests
    The authors declare that no competing interests exist.
  4. Mehdi Pirooznia

    National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, United States
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-4210-6458
  5. Hong Xu

    National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, United States
    For correspondence
    hong.xu@nih.gov
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-1423-1809

Funding

National Heart, Lung, and Blood Institute (Project Number: 1ZIAHL006153-07)

  • Hong Xu

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

Reviewing Editor

  1. Hugo J Bellen, Baylor College of Medicine, United States

Publication history

  1. Received: June 13, 2019
  2. Accepted: October 13, 2019
  3. Accepted Manuscript published: October 15, 2019 (version 1)
  4. Version of Record published: October 23, 2019 (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. Zong-Heng Wang
  2. Yi Liu
  3. Vijender Chaitankar
  4. Mehdi Pirooznia
  5. Hong Xu
(2019)
Electron transport chain biogenesis activated by a JNK-insulin-Myc relay primes mitochondrial inheritance in Drosophila
eLife 8:e49309.
https://doi.org/10.7554/eLife.49309

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