Project description:Authors:
Pia E. Ferle, Niklas Krause, Judith Koliwer, Joern Michael Voelker, Fabia Becker, Alexander Hillebrand, Leonie F. Schroeder, Stefanie Jaeger, Seby Edassery, Dali Liu, Nevan Krogan, Jeffrey N. Savas, Gabriele Fischer von Mollard and Michael Schwake
Project description:System-wide metabolic homeostasis is crucial for maintaining physiological functions of living organisms. Stable-isotope tracing metabolomics allows to unravel metabolic activity quantitatively by measuring the isotopically labeled metabolites, but has been largely restricted by coverage. Yet, delineating system-wide metabolic homeostasis at the whole-organism level remains non-trivial. Here, we develop a global isotope tracing metabolomics technology to measure labeled metabolites with a metabolome-wide coverage. Using Drosophila as an aging model organism, we probe the in vivo tracing kinetics with quantitative information on labeling patterns, extents and rates on a metabolome-wide scale. We curate a system-wide metabolic network to characterize metabolic homeostasis and disclose a system-wide loss of metabolic coordinations that impacts both intra- and inter-tissue metabolic homeostasis significantly during Drosophila aging. Importantly, we reveal an unappreciated metabolic diversion from glycolysis to serine metabolism and purine metabolism as Drosophila aging. The developed technology facilitates a system-level understanding of metabolic regulation in living organisms.