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Updated: Jul 31, 2025
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Exploring Mitochondrial Energy Metabolism of Single 3D Microtissue Spheroids Using Extracellular Flux Analysis
Published on: February 3, 2022
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Mitochondrial citrate metabolism and efflux regulate BeWo differentiation.
Renee M Mahr1, Snehalata Jena1, Sereen K Nashif1
1Department of Obstetrics, Gynecology and Women's Health, University of Minnesota, 420 Delaware Street SE, Minneapolis, MN, 55455, USA.
Scientific Reports
|May 6, 2023
Summary
Mitochondrial citrate metabolism is crucial for trophoblast differentiation. Disrupting the citrate transporter (CIC) impacts gene expression and histone acetylation, highlighting its role in placental health.
Area of Science:
- Cell Biology
- Biochemistry
- Reproductive Biology
Background:
- Cytotrophoblasts differentiate into syncytiotrophoblasts, a process vital for placental health.
- This differentiation involves metabolic and transcriptional reprogramming.
- Mitochondria are implicated in cellular differentiation events.
Purpose of the Study:
- To investigate the role of mitochondrial metabolism in trophoblast differentiation.
- To explore the function of citrate metabolism in regulating gene expression and histone acetylation during this process.
Main Methods:
- Utilized BeWo cell culture model for trophoblast differentiation.
- Employed untargeted metabolomics with stable isotope tracing.
- Conducted gene expression and histone acetylation analyses.
- Used CRISPR/Cas9 to disrupt the mitochondrial citrate transporter (CIC).
Main Results:
- Differentiation increased TCA cycle intermediates citrate and α-ketoglutarate.
- Citrate retention within mitochondria increased upon differentiation, with decreased CIC expression.
- CIC disruption impaired trophoblast differentiation, altering gene expression and histone acetylation.
- Acetate supplementation partially rescued gene expression changes.
Conclusions:
- Mitochondrial citrate metabolism is a key regulator of trophoblast differentiation.
- CIC plays a critical role in maintaining placental cell differentiation.
- Mitochondrial citrate influences histone acetylation and gene expression patterns essential for placental development.
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