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Published VersionCC BY V4.0, Open Access
Journal article
Proteomic Analysis of Placental Mitochondria Following Trophoblast Differentiation
Frontiers in Physiology, Vol.10, pp.1-10
2019
PMCID: PMC6933824
PMID: 31920727
Abstract
As gestation proceeds the human placenta is in a constant state of renewal and placental debris is released into the maternal circulation where it can trigger adverse physiological and immunological responses. Trophoblast cells of the placenta differentiate from mononuclear cytotrophoblast cells to fuse and form the syncytiotrophoblast, a multinuclear layer that covers the entire surface of the placenta. As part of this process there are significant changes to cellular cytoskeletal organization and organelle morphology. In this study we have examined the molecular changes that occur in mitochondria from these two cellular compartments and identified differential expression of key proteins that underpin changes in mitochondrial morphology, metabolism and function. Mitochondria were isolated for term placental tissue and separated according to size and density by sequential differential centrifugation. Isolated mitochondrial populations were then subjected to proteomics using HPLC separation of peptides and MS identification. Differential expression of proteins of interest was confirmed by western blots. Using a bioinformatics approach we also examined published protein databases to confirm our observations. In total 651 proteins were differentially regulated in mitochondria from cytotrophoblast versus syncytiotrophoblast. Of these 29 were statistically significant and chosen for subsequent analysis. These included subunits of ATP synthase that would affect ATP production and cristae structure, carbohydrate metabolizing enzymes phospoenolpyruvate carboxykinase-2, pyruvate carboxylase (PC) and pyruvate dehydrogenase (PDH), fatty acid metabolizing enzyme acyl-CoA dehydrogenase, stress responses such a glucose regulated protein-78 and protein disulfide isomerase, and mitochondrial dynamics proteins mitofusin 1 and 2. Placental cell biology and mitochondrial function is central to the pathogenesis of many gestational disorders such as preeclampsia, pre-term birth, fetal growth restriction and gestational diabetes. These studies show important shifts in mitochondrial metabolism and dynamics post trophoblast differentiation and provide key molecular targets for study in pathological pregnancies.
Details
- Title
- Proteomic Analysis of Placental Mitochondria Following Trophoblast Differentiation
- Authors
- Joshua J. Fisher (Author) - Griffith UniversityDaniel R. McKeating (Author) - Griffith UniversityJames S. Cuffe (Author) - The University of QueenslandTina Bianco-Miotto (Author) - The University of AdelaideOlivia J. Holland (Author) - Griffith UniversityAnthony Perkins (Corresponding Author) - Griffith University
- Publication details
- Frontiers in Physiology, Vol.10, pp.1-10
- Publisher
- Frontiers Research Foundation
- Date published
- 2019
- DOI
- 10.3389/fphys.2019.01536
- ISSN
- 1664-042X
- PMID
- 31920727; PMC6933824
- Copyright note
- © 2019 Fisher, McKeating, Cuffe, Bianco-Miotto, Holland and Perkins. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
- Organisation Unit
- School of Health; University of the Sunshine Coast, Queensland; School of Health and Behavioural Sciences - Legacy
- Language
- English
- Record Identifier
- 99685294702621
- Output Type
- Journal article
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