Electron transport chain biogenesis activated by a JNK-insulin-Myc relay primes mitochondrial inheritance in Drosophila
- 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).
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Myc regulation of ETC Biogenesis and mtDNA ReplicationNCBI Gene Expression Omnibus, GSE126997.
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dMyc_S2_cells_ChIP-seqNCBI Gene Expression Omnibus, GSE53560.
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dMyc_Kc167_cells_ChIP-seqNCBI Gene Expression Omnibus, GSE53559.
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dMyc_W3L_ChIP-seqNCBI Gene Expression Omnibus, GSE49774.
Article and author information
Author details
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.
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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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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