Electron tomography reveals mitochondrial network and cristae remodelling during cell differentiation in the human placenta
Year: 2026
Type: article
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.
Source: Nature Communications
Language: English
Subfield: Molecular Biology
Domain: Life Sciences
Open Access status: gold
Estimated APC paid: $6,990
Funders: Silicon Valley Community Foundation, Microsoft, GlaxoSmithKline, Queensland Health, Broad Institute, Royal Children's Hospital Foundation, Australian Government, Hunter Medical Research Institute, University of Wollongong, University of Melbourne, Medical Research Council, National Health and Medical Research Council, National Human Genome Research Institute, Medical Research Future Fund
Awards: A powerful web-based discovery platform for rare disease genetics, Building a foundation for equitable population-scale genomic medicine, G1992618992, Functional genomic studies of the human glutathione-S-transferase omega (GSTO) family, G2634154323, G4302627264, Advancing Treatment for Preterm Labour, Joint Center for Mendelian Genomics, The Australian Genomics Cardiovascular Genetic Disorders Flagship, G6416104534, G6687998774, A national large scale automated reanalysis program to increase rare disease diagnosis, G7193505718, G7953174984, G8565942559, G9000359386, G9000359812, G9000361543, Broad Institute Mendelian Genomic Research Center
OpenAlex ID: W4411177299