Dysregulated inter-mitochondrial crosstalk in glioblastoma cells revealed by in situ cryo-electron tomography

Glioblastomas (GBMs) are the most lethal primary brain tumors with limited survival, even under aggressive treatments. The current therapeutics for GBMs are flawed due to the failure to accurately discriminate between normal proliferating cells and distinctive tumor cells. Mitochondria are essential...

Full description

Saved in:
Bibliographic Details
Published inProceedings of the National Academy of Sciences - PNAS Vol. 121; no. 9; p. e2311160121
Main Authors Wang, Rui, Lei, Huan, Wang, Hongxiang, Qi, Lei, Liu, Yu'e, Liu, Yunhui, Shi, Yufeng, Chen, Juxiang, Shen, Qing-Tao
Format Journal Article
LanguageEnglish
Published United States National Academy of Sciences 27.02.2024
Subjects
Biological Sciences
Brain
Brain tumors
Cancer
Crosstalk
Glioblastoma
Glioblastoma cells
Mitochondria
Prediction models
Therapeutic applications
Tomography
Tumor cells
Tumors
glioblastoma
cryo-electron tomography
organelle crosstalk
mitochondria
Online AccessGet full text

Cover

More Information
Summary:Glioblastomas (GBMs) are the most lethal primary brain tumors with limited survival, even under aggressive treatments. The current therapeutics for GBMs are flawed due to the failure to accurately discriminate between normal proliferating cells and distinctive tumor cells. Mitochondria are essential to GBMs and serve as potential therapeutical targets. Here, we utilize cryo-electron tomography to quantitatively investigate nanoscale details of randomly sampled mitochondria in their native cellular context of GBM cells. Our results show that compared with cancer-free brain cells, GBM cells own more inter-mitochondrial junctions of several types for communications. Furthermore, our tomograms unveil microtubule-dependent mitochondrial nanotunnel-like bridges in the GBM cells as another inter-mitochondrial structure. These quantified inter-mitochondrial features, together with other mitochondria-organelle and intra-mitochondrial ones, are sufficient to distinguish GBM cells from cancer-free brain cells under scrutiny with predictive modeling. Our findings decipher high-resolution inter-mitochondrial structural signatures and provide clues for diagnosis and therapeutic interventions for GBM and other mitochondria-related diseases.
Bibliography:ObjectType-Article-1
SourceType-Scholarly Journals-1
ObjectType-Feature-2
content type line 23
Edited by Frank Winkler, Deutsches Krebsforschungszentrum, Heidelberg, Germany; received July 1, 2023; accepted January 18, 2024 by Editorial Board Member Rakesh K. Jain
1R.W. and H.L. contributed equally to this work.
ISSN:0027-8424
1091-6490
1091-6490
DOI:10.1073/pnas.2311160121