"The metabolic changes we observed freed up the CoA to make ATP," said Suzanne Jackowski, Ph.D., a member of the St. Jude Infectious Diseases department and the paper's senior author. "Our study provides the first detailed look at how the cell shifts genetic gears to respond to a significant change in its ability to carry on its daily metabolic chores."
The St. Jude study also showed that PanK controls the concentration of CoA in the cell depending on how much is needed and where it is needed. Previous studies at St. Jude showed that four different forms of PanK exist in different places in the cell and each one can be inhibited by rising levels of CoA. This allows the cell to increase or decrease CoA levels in specific locations, depending on the amount of CoA needed.
These findings not only give researchers a detailed look at how the cell responds to a significant reduction in the concentration of a critical molecule. The alterations in the activity of certain genes and enzymes also serve as a model for the milder disruption of CoA levels that may underlie a brain disorder called pantothenate-kinase-associated neurodegeneration (PKAN). PKAN is a hereditary disorder caused by mutations in PanK that may lead to a deficiency of CoA in brain mitochondria. Previously, this group of St. Jude researchers showed how specific mutations in one form of PanK disable this enzyme, which in turn would reduce CoA production and cause PKAN (http://www.st
Contact: Summer Freeman
St. Jude Children's Research Hospital