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Publication : Functional mitochondrial respiration is essential for glioblastoma tumour growth.

First Author  Brisudova P Year  2025
Journal  Oncogene Volume  44
Issue  30 Pages  2588-2603
PubMed ID  40325182 Mgi Jnum  J:375486
Mgi Id  MGI:8226911 Doi  10.1038/s41388-025-03429-6
Citation  Brisudova P, et al. (2025) Functional mitochondrial respiration is essential for glioblastoma tumour growth. Oncogene 44(30):2588-2603
abstractText  Horizontal transfer of mitochondria from the tumour microenvironment to cancer cells to support proliferation and enhance tumour progression has been shown for various types of cancer in recent years. Glioblastoma, the most aggressive adult brain tumour, has proven to be no exception when it comes to dynamic intercellular mitochondrial movement, as shown in this study using an orthotopic tumour model of respiration-deficient glioblastoma cells. Although confirmed mitochondrial transfer was shown to facilitate tumour progression in glioblastoma, we decided to investigate whether the related electron transport chain recovery is necessary for tumour formation in the brain. Based on experiments using time-resolved analysis of tumour formation by glioblastoma cells depleted of their mitochondrial DNA, we conclude that functional mitochondrial respiration is essential for glioblastoma growth in vivo, because it is needed to support coenzyme Q redox cycling for de novo pyrimidine biosynthesis controlled by respiration-linked dihydroorotate dehydrogenase enzyme activity. We also demonstrate here that astrocytes are key mitochondrial donors in this model.
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