The heart is one of the most energy demanding tissues and hydrolyses 6 kg adenosine triphosphate (ATP) per day. 95% of its energy demand is covered by oxidative phosphorylation in mitochondria. Besides their role in energy conversion, mitochondria have multiple functions in metabolism, like the citric acid cycle, the urea cycle, the metabolism of amino acids and lipids and the biogenesis of heme and iron-sulfur clusters. Dysfunctional mitochondria, which cannot provide the required energy, often cause cardiac diseases. Mitochondrial diseases are a heterogeneous group of disorders, prevalent in approximately one in 5000 births. Mitochondrial dysfunctions can be caused either by mutations in the mitochondrial genome or by mutations in nuclear-encoded proteins.

Mitochondria are surrounded by two membranes, which play an essential role in many aspects of mitochondrial physiology. The inner membrane of mitochondria forms cristae structures, which harbor the respiratory chain. The respiratory chain converts the flux of electrons from the oxidative metabolism into a proton gradient that fuels ATP production at the ATP synthase. Mitochondrial membranes are characterized by a high content of the phospholipid cardiolipin (CL), which is associated to many essential mitochondrial functions. Changes in the CL pool are associated with a large number of cardiac diseases. A loss of the predominant species of CL was found in patients with dilated cardiomyopathy, in pediatric patients diagnosed with idiopathic dilated cardiomyopathy (IDC) and in ischemic (ICM) or dilated (DCM) cardiomyopathy.

We are interested in the pathological mechanisms through which mitochondrial dysfunctions promote the development of cardiac diseases. To elucidate the role of CL in the pathogenesis of heart disease, we study Barth Syndrome (BTHS), an inherited form of cardiomyopathy, associated with neutropenia, growth retardation and skeletal myopathy. BTHS is caused by a mutation in an enzyme required for the maturation of CL after its initial biogenesis. We use different models to study dysfunctions of the respiratory chain and changes in the metabolism of cardiomyocytes. We are interested in how defects in key mitochondrial functions like respiration and metabolism may affect cardiac function. In recent years it became clear that mitochondria also function as signaling hubs for many cellular pathways. We are interested how fundamental cellular signaling pathways are affected by dysfunctional mitochondria.