MITIG has tackled how glioma communicate and acquire functional mitochondria to reconfigure their metabolism, as these organelles are master regulators of respiration and processing of nutrients in the cell. MITIG has set a wide range of dedicated and innovative genetic, pharmacological, ultrastructural, morphological and functional approaches and analyses. As a result, we show that glioma cells acquire mitochondria through their intercellular transfer or importation from neighbour cells, highlighting their acquisition from astrocytes as donors. The incorporation of exogenous mitochondria reconfigures the morphology and ultrastructure of the native mitochondrial network in acceptor glioma cells. Importantly, exogenous mitochondrial DNA and proteins integrate the composition of the whole native network, resulting in a diverted mitochondrial function. Consequently, glioma cells rewire the way they respire and derive nutrients towards a processing control exerted by mitochondria, at the expense of other metabolic paths that become less relevant for glioma development. The change in the respiration and fuel usage by glioma cells deeply impact their fate, whereby the survival of tumour cells is shortcut by interfering with the acquisition of mitochondria, causing a major impact in the development of brain tumours. Altogether, MITIG has tackled a key path underscoring the communication and rewiring of mitochondrial content, respiration and metabolism that leads to glioblastoma progression. The results arising from MITIG, disseminated through the project webpage and several contributions in media, meetings and scientific manuscripts, foresees major biomedical applications in glioblastoma oncology.
