Cardiolipin Requirement for Mitochondrial Calcium Import
Vishal Gohil, PhD, Associate Professor, Texas A&M University, College Station, TX
The clinical abnormalities observed in Barth syndrome patients are caused by perturbations in mitochondria, the powerhouse of the cell. These perturbations have been traced to defects in the biosynthesis of cardiolipin, a building block of the mitochondrial membranes. Although decades of research have identified critical roles of cardiolipin in different mitochondrial functions, we still do not know the full spectrum of cardiolipin-dependent mitochondrial functions that may contribute to Barth syndrome disease pathology. One important factor that controls mitochondrial energy production is calcium signaling. Because mitochondrial calcium import machinery is localized to mitochondrial membrane, we reasoned that cardiolipin deficiency might disrupt calcium import. Indeed, our preliminary results show that the abundance and activity of mitochondrial calcium uniporter, a highly selective calcium channel, is decreased in cellular models of Barth syndrome. This key finding forms the basis of our hypothesis that depletion of cardiolipin levels could impair mitochondrial calcium signaling. We will test this hypothesis by determining whether calcium-signaling dependent mitochondrial bioenergetics is perturbed in Barth syndrome patient cells and heart tissue. These studies will uncover the role of mitochondrial calcium signaling in Barth syndrome disease pathology, which will provide a new way to understand and treat this debilitating disease.