Yuen-Li Chung1, Gigin Lin1, Helen Troy1, Anne-Christine Wong Te Fong1, L. E. Jackson1, Deborah K. Hill1, Matthew Orton1, Dow-Mu Koh1, Simon P. Robinson1, Ian R. Judson2, John R. Griffiths3, Martin O. Leach1, Thomas R. Eykyn1
1CR-UK & EPSRC Cancer Imaging Centre, Institute of Cancer Research & Royal Marsden Hospital, Sutton, Surrey, United Kingdom; 2CR-UK Centre for Cancer Therapeutics, Institute of Cancer Research & Royal Marsden Hospital, Sutton, Surrey, United Kingdom; 3Li Ka Shing Centre, CR-UK Cambridge Research Institute, Cambridge, United Kingdom
Autophagy is a cellular degradation response to starvation or stress whereby cellular proteins, organelles and cytoplasm are engulfed, digested and recycled to sustain cellular metabolism. We have investigated the effects of autophagy on TCA cycle activation using 1-13C-pyruvate DNP 13C-MRS. Autophagy was induced in three cancer cell lines by starvation, dichloroacetate and PI103 treatment. A significant reduction in the rate of labelled [1-13C] pyruvate to lactate exchange (and unpolarised lactate production) was associated with autophagy, rather than apoptosis or necrosis. A reduction in lactate production as measured by DNP 13C-MRS, and unchanged NAD+, may provide a non-invasive surrogate biomarker of autophagy.