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.

• MeSH
• Astrocytes metabolism   pathology   MeSH
• Cell Respiration MeSH
• Dihydroorotate Dehydrogenase MeSH
• Glioblastoma * pathology   metabolism   genetics   MeSH
• Humans MeSH
• DNA, Mitochondrial genetics   MeSH
• Mitochondria * metabolism   MeSH
• Mice MeSH
• Cell Line, Tumor MeSH
• Brain Neoplasms * pathology   metabolism   genetics   MeSH
• Oxidoreductases Acting on CH-CH Group Donors metabolism   MeSH
• Cell Proliferation MeSH
• Electron Transport MeSH
• Ubiquinone metabolism   MeSH
• Animals MeSH
• Check Tag
• Humans MeSH
• Mice MeSH
• Animals MeSH
• Publication type
• Journal Article MeSH
• Names of Substances
• Dihydroorotate Dehydrogenase MeSH
• DNA, Mitochondrial MeSH
• Oxidoreductases Acting on CH-CH Group Donors MeSH
• Ubiquinone MeSH