DC3
Establish dynamics and maintenance of subcellular CoA pools in cell, mouse, and fly models
Background: Homeostasis of CoA pools is essential. This is underscored by the knowledge that genetic errors in genes coding for CoA biosynthesis enzymes lead to severe neurodegenerative and cardiac diseases. Established cell, mouse and fly models exist that recapitulate the symptoms of these CoA-linked diseases. How subcellular CoA levels are regulated and how this is affected by these genetic defects is unknown. This knowledge is important to find treatments for these diseases.
Objectives: (1) Determine the presence of CoA and CoA precursors such as 4’-phosphopantetheine in subcellular compartments of various control cells and tissues. (2) Determine CoA (precursor) levels in various models of CoA-linked diseases with and without molecules which have treatment potential. (3) Establish effects on other hub molecule levels (NAD) in the CoA-disease models.