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 (Ca²⁺) released from the sarcoplasmic reticulum drives sarcomeric contraction. At the same time, Ca²⁺ 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 Ca²⁺ 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.

中文翻译：

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巴特综合征的机械能量方面

心脏等需要能量的器官强烈依赖于线粒体中的氧化磷酸化。氧化磷酸化受位于线粒体内膜的呼吸链控制。线粒体内膜是唯一具有大量磷脂心磷脂的细胞膜，并且发现心磷脂直接与许多必需的蛋白质复合物相互作用，包括呼吸链复合物 I 至 V。心磷脂生物发生中的遗传缺陷导致 Barth综合征，与心肌病、骨骼肌病、中性粒细胞减少和生长迟缓有关。能量转换依赖于还原当量，这些当量由克雷布斯循环中的氧化代谢补充。Barth 综合征中的心磷脂缺乏也会影响克雷布斯循环活动，代谢物转运和线粒体形态。在兴奋-收缩耦合过程中，钙（Ca²⁺ ) 从肌质网释放，驱动肌节收缩。同时，Ca ²⁺流入线粒体驱动克雷布斯循环脱氢酶的激活和还原当量的再生。减少当量不仅对于能量转换至关重要，而且对于维持氧化还原缓冲液也是必不可少的，这是对活性氧 (ROS) 进行解毒所必需的。CL 的缺陷也可能影响 Ca ²⁺进入线粒体，从而阻碍能量供需匹配，也影响 ROS 的解毒。在这里，我们回顾了心磷脂缺乏对 Barth 综合征线粒体功能的影响，并讨论了潜在的治疗策略。