Stefan Kempa: Missing Links: Metabolic Circuits in Regulatory Networks

Dr. Stefan Kempa
BIMSB (Berlin Institute for Medical Systems Biology at the MDC Berlin Buch, Berlin, Germany)

Missing links: metabolic circuits in regulatory networks

The central metabolism is the principal source of energy and building blocks for cell growth and survival. It is highly flexible and adjusted to the physiological program of the cell, organ and organism. In a healthy state cellular metabolism is tightly regulated to guaranty physiological function but also efficient usage of available recourses. Metabolic dys-regulations are cause or response to many diseases. However, the underlying mechanisms leading to metabolic dys-functions are not well understood.
To gain deeper insights in the dynamics of metabolism we adapted available techniques for proteome and metabolome analyses, as well as stable isotope labeling. We observed that metabolic activities are not necessarily reflected in the abundance of transcripts, proteins or even in the steady-state levels of metabolites. Beyond being regulated simply by the expression levels of enzymes, the cellular metabolic pattern is influenced also by the isoform composition of the enzymatic network and its regulatory properties.
With our experiments we aimed to elucidate the metabolic dynamics of human cells in response to glucose and oxygen, the mayor nutrients. Surprisingly, we found that the rate of lactate production, a measure of glycolytic activity, does not reflect cell growth. We speculate that further metabolic pathways support proliferation of cancer cells. In a collaborative project we were able to decode the regulatory mode of a central energy sensing pathway in regulating mitochondrial metabolism. We found a new regulatory links beyond transcriptional regulation.