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Intercellular mitochondrial transfer in glioblastoma

40 months
Approved budget:
Professor Michael Berridge
Health issue:
Cancer (oncology)
Proposal type:
Lay summary
Mitochondrial movement between cells has been demonstrated in cell culture, and we have shown that tumour cells without a mitochondrial (mt) genome acquire mtDNA from surrounding normal cells leading to recovery of respiration, tumour growth, and metastasis. These unprecedented results raise questions about whether intercellular mitochondrial transfer is a normal “silent” physiological process since mtDNA damage that contributes to compromised respiratory function occurs in many cancers and is an inevitable consequence of anticancer drug treatments and radiation. We have developed a mouse model of glioblastoma that lacks mtDNA and will determine whether these cells form brain tumours and if so, whether mitochondrial acquisition from brain cells is involved. We will also damage mtDNA in glioblastoma cells and investigate the relationship between this damage, mitochondrial acquisition from normal brain cells, and tumour formation. Mitochondrial transfer to tumour cells with mitochondrial genome damage could be widely relevant to tumour biology and treatment.