Medizinische Universität Graz Austria/Österreich - Forschungsportal - Medical University of Graz
Gewählte Publikation:
Depaoli, M.
Real-time imaging of mitochondrial ATP dynamics allows metabolic profiling of individual cells
PhD-Studium (Doctor of Philosophy); Humanmedizin; [ Dissertation ] ; 2018. pp. 71
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- Autor*innen der Med Uni Graz:
- Depaoli Maria Rosa
- Betreuer*innen:
- Graier Wolfgang
- Malli Roland
- Altmetrics:
- Abstract:
- Many physiological and pathophysiological processes are accompanied by alterations in the energy metabolism of a cell. Such changes particularly affect ATP generating pathways. In this work genetically encoded fluorescent ATP sensors were used to measure ATP dynamics on the level of individual cell. Mitochondrial ATP levels were found to be most dynamic, with cell-type specific features. HeLa cells, as a model for cancer cells, produce ATP predominantly via aerobic glycolysis, while their mitochondria tend to consume ATP rather than generate it via oxidative phosphorylation. Insulin producing beta cells (INS1, MIN-6), on the other hand, mainly rely on mitochondrial ATP production via oxidative phosphorylation. These results demonstrate, that mitochondrial ATP measurements can be used for the metabolic characterization of different cell types, as it was done in this study for different cancer (H1299, A548, Calu-3, SkBr3, MCF7, MDA-MB231, SH-SY5Y) and non-cancer (wild-type and Mfn2 knockout MEFs) cells. Furthermore, mitochondrial ATP measurements in HeLa cells revealed a tight coupling of the mitochondrial ATP pool with mitochondria-associated hexokinase enzymes. Altogether, the findings presented in this work add new perspectives on cellular bioenergetics and demonstrate that live-cell imaging of mitochondrial ATP dynamics is a powerful tool to evaluate the metabolic flexibility and heterogeneity of cells and cell populations.