Journal article
Electron tomography reveals mitochondrial network and cristae remodelling during cell differentiation in the human placenta
Nature Communications, Vol.Advanced access(1)
08-Jul-2026
PMCID: PMC13473558
PMID: 42420306
Abstract
Mitochondria adapt their structure through fusion and fission, yet how their morphology and cristae architecture change as cells differentiate remains unclear. The human placenta is a valuable model for studying mitochondrial diversity within a single tissue. As epithelial trophoblast cells of the placenta differentiate, their accompanying mitochondria morphologically and functionally transform. We use array tomography to characterise mitochondrial volume and network complexity. Cryo-electron tomography reveals two distinct subpopulations of mitochondria within preparations enriched for progenitor cytotrophoblasts, and a singular, homogeneous population in the differentiated syncytiotrophoblast. We showcase the 3D topology of individual cristae through a standardised metric of "curvedness". Proteomic analysis of isolated mitochondria identifies reduced levels of proteins involved in mitochondrial dynamics and cristae organisation complexes in the syncytiotrophoblast, accompanied by variations in electron transport chain subunits, ATP synthase, and supercomplex components. This study highlights the advantages of combining multimodal imaging with proteomic analyses, to elucidate the process of mitochondrial morphology and cristae architecture remodelling as cells differentiate.
Details
- Title
- Electron tomography reveals mitochondrial network and cristae remodelling during cell differentiation in the human placenta
- Authors
- Siddharth Acharya - Hunter Medical Research InstituteEric Hanssen - The University of MelbourneVeronica B Botha - Hunter Medical Research InstituteTia M Smith - Hunter Medical Research InstituteSahan Jayatissa - University of AucklandZlatan Trifunovic - The University of MelbourneLucy A Bartho - Mercy Hospital for WomenJohn E Schjenken - Hunter Medical Research InstituteTu'uhevaha J Kaitu'u-Lino - Mercy Hospital for WomenAnthony V Perkins - University of the Sunshine CoastJoanna L James - University of AucklandKirsty G Pringle - University of Newcastle AustraliaJames C Bouwer - University of WollongongRoger Smith - Hunter Medical Research InstituteJoshua J Fisher (Corresponding Author) - Hunter Medical Research Institute
- Publication details
- Nature Communications, Vol.Advanced access(1)
- Publisher
- Nature Publishing Group
- DOI
- 10.1038/s41467-026-75408-8
- ISSN
- 2041-1723
- PMID
- 42420306; PMC13473558
- Copyright note
- This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/.
- Data Availability
- The array tomography data generated in this study have been deposited in the European Bioinformatics Institute (EBI) BioImage Archive under accession code S-BIAD3408 [https://www.ebi.ac.uk/biostudies/bioimages/studies/S-BIAD3408]. The cryo-ET tilt series and reconstructed tomograms are available on EBI BioImage Archive under accession code S BIAD3409 [https://www.ebi.ac.uk/biostudies/bioimages/studies/S-BIAD3409]. This study performed an in silico analysis of a legacy proteomics dataset, therefore LC-MS data is included in the Source Data file, and .RAW LC-MS acquisition files are available upon reasonable request.
- Grants
- Grant note
- John Hunter Hospital Charitable Trust, Newcastle Permanent Emerging Innovator Award and Hunter Medical Research Institute.
- Organisation Unit
- School of Health
- Language
- English
- Record Identifier
- 991246197002621
- Output Type
- Journal article
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