Integrative consequences of defective mitochondrial Ca2+ uptake in Barth syndrome (A13)

• Subject Area: Molecular Biology and Physiology of Neurons and Glial Cells
• Term: from 2011 to 2022
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 157660137

Barth syndrome causes immune deficiency, muscle fatigue and heart failure in infant boys. This is caused by a defect in the gene encoding Tafazzin (Taz), which catalyzes the final step in the synthesis of cardiolipin, a key component of the inner mitochondrial membrane. We observed that in the hearts of Taz-deficient mice, mitochondrial Ca2+ uptake is compromised due to a loss of the Ca2+ uniporter protein. Since mitochondrial Ca2+ is required to match ATP supply to demand and to regenerate the antioxidative capacity, we will investigate whether the Ca2+ defect causes energetic deficit and oxidative stress in Taz-deficient mice, with the goal to find novel treatment options for Barth syndrome, a so far orphan disease.

• DFG Programme: Collaborative Research Centres
• Subproject of: SFB 894: Ca2+-Signalling: Molecular Mechanisms and Integrative Functions
• Applicant Institution: Universität des Saarlandes
• Project Heads: Professor Dr. Christoph Maack; Professorin Dr. Leticia Prates Roma, Ph.D.