Dynamic redox balance directs the oocyte-to-embryo transition via developmentally controlled reactive cysteine changes
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 mat...
| Main Authors: | , , , , , , |
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| Format: | Article |
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National Academy of Sciences (U.S.)
2019
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| Online Access: | https://hdl.handle.net/1721.1/121332 |
| _version_ | 1826208204631048192 |
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| author | Petrova, Boryana Liu, Keke Tian, Caiping Kitaoka, Maiko Freinkman, Elizaveta Yang, Jing Orr-Weaver, Terry |
| author2 | Massachusetts Institute of Technology. Department of Biology |
| author_facet | Massachusetts Institute of Technology. Department of Biology Petrova, Boryana Liu, Keke Tian, Caiping Kitaoka, Maiko Freinkman, Elizaveta Yang, Jing Orr-Weaver, Terry |
| author_sort | Petrova, Boryana |
| collection | MIT |
| description | 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. |
| first_indexed | 2024-09-23T14:02:10Z |
| format | Article |
| id | mit-1721.1/121332 |
| institution | Massachusetts Institute of Technology |
| last_indexed | 2024-09-23T14:02:10Z |
| publishDate | 2019 |
| publisher | National Academy of Sciences (U.S.) |
| record_format | dspace |
| spelling | mit-1721.1/1213322022-10-01T18:44:12Z Dynamic redox balance directs the oocyte-to-embryo transition via developmentally controlled reactive cysteine changes Petrova, Boryana Liu, Keke Tian, Caiping Kitaoka, Maiko Freinkman, Elizaveta Yang, Jing Orr-Weaver, Terry Massachusetts Institute of Technology. Department of Biology 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. 2019-06-17T19:17:05Z 2019-06-17T19:17:05Z 2018-08 2018-05 2019-03-25T15:37:57Z Article http://purl.org/eprint/type/JournalArticle 0027-8424 1091-6490 https://hdl.handle.net/1721.1/121332 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 http://dx.doi.org/10.1073/PNAS.1807918115 Proceedings of the National Academy of Sciences Article is made available in accordance with the publisher's policy and may be subject to US copyright law. Please refer to the publisher's site for terms of use. application/pdf National Academy of Sciences (U.S.) PNAS |
| spellingShingle | Petrova, Boryana Liu, Keke Tian, Caiping Kitaoka, Maiko Freinkman, Elizaveta Yang, Jing Orr-Weaver, Terry Dynamic redox balance directs the oocyte-to-embryo transition via developmentally controlled reactive cysteine changes |
| title | Dynamic redox balance directs the oocyte-to-embryo transition via developmentally controlled reactive cysteine changes |
| title_full | Dynamic redox balance directs the oocyte-to-embryo transition via developmentally controlled reactive cysteine changes |
| title_fullStr | Dynamic redox balance directs the oocyte-to-embryo transition via developmentally controlled reactive cysteine changes |
| title_full_unstemmed | Dynamic redox balance directs the oocyte-to-embryo transition via developmentally controlled reactive cysteine changes |
| title_short | Dynamic redox balance directs the oocyte-to-embryo transition via developmentally controlled reactive cysteine changes |
| title_sort | dynamic redox balance directs the oocyte to embryo transition via developmentally controlled reactive cysteine changes |
| url | https://hdl.handle.net/1721.1/121332 |
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