TY  - JOUR
A1  - Dudek, Jan
A1  - Maack, Christoph
T1  - Mechano-energetic aspects of Barth syndrome
T2  - Journal of Inherited Metabolic Disease
N2  - Energy-demanding organs like the heart are strongly dependent on oxidative phosphorylation in mitochondria. Oxidative phosphorylation is governed by the respiratory chain located in the inner mitochondrial membrane. The inner mitochondrial membrane is the only cellular membrane with significant amounts of the phospholipid cardiolipin, and cardiolipin was found to directly interact with a number of essential protein complexes, including respiratory chain complexes I to V. An inherited defect in the biogenesis of cardiolipin causes Barth syndrome, which is associated with cardiomyopathy, skeletal myopathy, neutropenia and growth retardation. Energy conversion is dependent on reducing equivalents, which are replenished by oxidative metabolism in the Krebs cycle. Cardiolipin deficiency in Barth syndrome also affects Krebs cycle activity, metabolite transport and mitochondrial morphology. During excitation-contraction coupling, calcium (Ca\(^{2+}\)) released from the sarcoplasmic reticulum drives sarcomeric contraction. At the same time, Ca\(^{2+}\) influx into mitochondria drives the activation of Krebs cycle dehydrogenases and the regeneration of reducing equivalents. Reducing equivalents are essential not only for energy conversion, but also for maintaining a redox buffer, which is required to detoxify reactive oxygen species (ROS). Defects in CL may also affect Ca\(^{2+}\) uptake into mitochondria and thereby hamper energy supply and demand matching, but also detoxification of ROS. Here, we review the impact of cardiolipin deficiency on mitochondrial function in Barth syndrome and discuss potential therapeutic strategies.
KW  - Barth syndrome
KW  - respiratory chain
KW  - reactive oxygen species
KW  - cardiolipin
KW  - mitochondria
Y1  - 2022
UR  - https://opus.bibliothek.uni-wuerzburg.de/frontdoor/index/index/docId/25751
UR  - https://nbn-resolving.org/urn:nbn:de:bvb:20-opus-257512
VL  - 45
IS  - 1
ER  -