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タイトル | Dysregulated inter-mitochondrial crosstalk in glioblastoma cells revealed by in situ cryo-electron tomography. |
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ジャーナル・号・ページ | Proc Natl Acad Sci U S A, Vol. 121, Issue 9, Page e2311160121, Year 2024 |
掲載日 | 2024年2月27日 |
著者 | Rui Wang / Huan Lei / Hongxiang Wang / Lei Qi / Yu'e Liu / Yunhui Liu / Yufeng Shi / Juxiang Chen / Qing-Tao Shen / |
PubMed 要旨 | 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 ...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. |
リンク | Proc Natl Acad Sci U S A / PubMed:38377189 / PubMed Central |
手法 | EM (トモグラフィー) |
構造データ | EMDB-39012: Representative tomogram of primary glioblastoma stem cell with circular inter-mitochondrial junctions. EMDB-39015: Representative tomogram of microglia cell with nanotunnel-like structures resembling mitochondrial fission. EMDB-39019: Representative tomogram of glioblastoma cell with nanotunnel-like structure and inter-mitochondrial junction. EMDB-39021: Representative tomogram of normal human astrocyte with nanotunnel-like structure which is an extension of the mitochondrial outer membrane. EMDB-39023: Representative tomogram of primary glioblastoma differentiated cell with parallel inter-mitochondrial junction. EMDB-39024: Representative tomogram of primary glioblastoma stem cell with clustered mitochondria bearing various long-short axis ratios. |
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