Grant: Operating Grant

Cardiolipin is an important phospholipid (phosphorus containing lipid or fat) found in mammalian cells. It is the major phospholipid found in mitochondria (a cellular organelle responsible for the synthesis of energy for the cell to function). Some enzymes (proteins which synthesize or breakdown compounds) in mitochondria that produce energy have an absolute requirement for cardiolipin. Cardiolipin contains four fatty acid side chains that are important for activation of these mitochondrial enzymes. My research program focuses on examining how cardiolipin is remodelled, that is, how are these fatty acids placed on the cardiolipin molecule. We know that the remodelling of cardiolipin is defective in children with Barth Syndrome, a rare genetic disease. There are many different mutations that cause Barth Syndrome. One of the enzymes involved in cardiolipin remodelling is called MLCL AT-1. In this application we are proposing to characterize this enzyme and examine whether increasing the amount of this enzyme in cells from Barth Syndrome patients with different mutations restores cardiolipin levels and mitochondrial function. We also propose to examine how MLCL AT-1 functions in regulating the level and activity of other cardiolipin remodelling enzyme.