Dynamic redox balance directs the oocyte-to-embryo transition via developmentally controlled reactive cysteine changes
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E7978.full.pdf
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Author(s)
Petrova, Boryana
Liu, Keke
Tian, Caiping
Kitaoka, Maiko
Freinkman, Elizaveta
Yang, Jing
Orr-Weaver, Terry
Date Issued
August 2018
Journal
Proceedings of the National Academy of Sciences
Publisher
National Academy of Sciences (U.S.)
Citation
Petrova, Boryana et al. “Dynamic Redox Balance Directs the Oocyte-to-Embryo Transition via Developmentally Controlled Reactive Cysteine Changes.” Proceedings of the National Academy of Sciences 115, 34 (August 2018): E7978–E7986 © 2018 National Academy of Sciences
Version
Final published version
Abstract
The metabolic and redox state changes during the transition from an arrested oocyte to a totipotent embryo remain uncharacterized. Here, we applied state-of-the-art, integrated methodologies to dissect these changes in Drosophila. We demonstrate that early embryos have a more oxidized state than mature oocytes. We identified specific alterations in reactive cysteines at a proteome-wide scale as a result of this metabolic and developmental transition. Consistent with a requirement for redox change, we demonstrate a role for the ovary-specific thioredoxin Deadhead (DHD). dhd-mutant oocytes are prematurely oxidized and exhibit meiotic defects. Epistatic analyses with redox regulators link dhd function to the distinctive redox-state balance set at the oocyte-to-embryo transition. Crucially, global thiol-redox profiling identified proteins whose cysteines became differentially modified in the absence of DHD. We validated these potential DHD substrates by recovering DHD-interaction partners using multiple approaches. One such target, NO66, is a conserved protein that genetically interacts with DHD, revealing parallel functions. As redox changes also have been observed in mammalian oocytes, we hypothesize a link between developmental control of this cell-cycle transition and regulation by metabolic cues. This link likely operates both by general redox state and by changes in the redox state of specific proteins. The redox proteome defined here is a valuable resource for future investigation of the mechanisms of redox-modulated control at the oocyte-to-embryo transition.
MIT Department
Massachusetts Institute of Technology. Department of Biology
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DOI of Published Version
https://doi.org/10.1073/PNAS.1807918115
