The study focussed on the effect that autophagy modulation has on mitochondrial bioenergetics in the context of cancer metabolism, entailing extensive characterisation of mitochondrial dynamics and morphometrics. We developed a unique photoactivation protocol that more accurately determines the rate at which mitochondrial fission and fusion occurs. Image processing algorithms were also constructed in Wolfram Mathematica to better quantify the morphological changes within mitochondrial networks. Correlating these data sets with changes in autophagic flux and mitochondrial respiration, we determined that a state of intermediate connectivity exists in mitochondrial networks when autophagic degradation is impaired. During this maladaptive state, brain cancer cells could be effectively sensitized to undergo cell death, indicating the importance of both autophagic flux and mitochondrial bioenergetics in upholding tumour metabolism. 

Stellenbosch University