Essential activities of Tafazzin that are independent of cardiolipin remodeling

William T. Pu, MD, Professor, Boston Children's Hospital, Boston, MA

Award - $50,000 over 1-year period

Barth syndrome is caused by mutation of Tafazzin (TAZ), an enzyme needed to properly produce cardiolipin, an essential component of mitochondria. Mitochondria are needed in all cells, especially muscle cells, for metabolism and energy production. In Barth syndrome mice, most mice die during the neonatal period. Gene therapy with a virus that replaces the mutant TAZ with normal TAZ prevented neonatal death and allowed most mice to live to adulthood. Unexpectedly, replacement of mutant TAZ with naturally occurring forms of TAZ that are unable to produce cardiolipin ("variant TAZ") still rescued some Barth mice from neonatal death. This suggests that TAZ has additional functions beyond its ability to produce cardiolipin. We hypothesize that these additional functions are due to TAZ protein interacting with other proteins. Here we will measure mitochondrial activity of Barth cells treated with normal or variant TAZ. We will identify other proteins that interact with normal and variant TAZ. These studies will allow us to discover TAZ activities that are independent of its ability to make cardiolipin.