Dudek Jan, Maack Christoph
Department of Cellular Biochemistry, University Medical Center Göttingen, 37073 Göttingen, Germany.
Klinik für Innere Medizin III, Universitätsklinikum des Saarlandes, 66421 Homburg/Saar, Germany.
Cardiovasc Res. 2017 Mar 15;113(4):399-410. doi: 10.1093/cvr/cvx014. Epub 2017 Feb 2.
Barth syndrome (BTHS) is an inherited form of cardiomyopathy, caused by a mutation within the gene encoding the mitochondrial transacylase tafazzin. Tafazzin is involved in the biosynthesis of the unique phospholipid cardiolipin (CL), which is almost exclusively found in mitochondrial membranes. CL directly interacts with a number of essential protein complexes in the mitochondrial membranes including the respiratory chain, mitochondrial metabolite carriers, and proteins, involved in shaping mitochondrial morphology. Here we describe, how in BTHS CL deficiency causes changes in the morphology of mitochondria, structural changes in the respiratory chain, decreased respiration, and increased generation of reactive oxygen species. A large number of cellular and animal models for BTHS have been established to elucidate how mitochondrial dysfunction induces sarcomere disorganization and reduced contractility, resulting in dilated cardiomyopathy in vivo.
巴斯综合征（BTHS）是一种遗传性心肌病，由编码线粒体转酰基酶塔法兹蛋白的基因突变引起。塔法兹蛋白参与独特磷脂心磷脂（CL）的生物合成，而心磷脂几乎只存在于线粒体膜中。CL直接与线粒体膜中的许多重要蛋白质复合物相互作用，包括呼吸链、线粒体代谢物载体以及参与线粒体形态塑造的蛋白质。在此我们描述了在BTHS中CL缺乏如何导致线粒体形态改变、呼吸链结构变化、呼吸减少以及活性氧生成增加。已经建立了大量BTHS的细胞和动物模型，以阐明线粒体功能障碍如何诱导线粒体肌小节紊乱和收缩力降低，从而在体内导致扩张型心肌病。
