Damschroder Deena, Reynolds Christian, Wessells Robert
Deparment of Physiology, Wayne State University School of Medicine, Detroit, Michigan.
Department of Emergency Medicine, Wayne State University School of Medicine, Detroit, Michigan.
Physiol Rep. 2018 Feb;6(3). doi: 10.14814/phy2.13604.
Cardiolipin (CL) is a mitochondrial phospholipid that helps maintain normal structure of the inner mitochondrial membrane and stabilize the protein complexes of the electron transport chain to promote efficient ATP synthesis. Tafazzin, an acyl-transferase, is required for synthesis of the mature form of CL. Mutations in the tafazzin (TAZ) gene are associated with a human disorder known as Barth syndrome. Symptoms of Barth syndrome often include muscle weakness and exercise intolerance. Previous work demonstrates that Drosophila Taz mutants exhibit motor weakness, as measured by reduced flying and climbing abilities. However, Drosophila TAZ mutants' baseline endurance or response to endurance exercise training has not been assessed. Here, we find that TAZ mutants have reduced endurance and do not improve following a stereotypical exercise training paradigm, indicating that loss of TAZ function leads to exercise intolerance in Drosophila. Although cardiac phenotypes are observed in human Barth syndrome patients, TAZ mutants had normal resistance to cardiac pacing. In the future, endurance may be a useful screening tool to identify additional genetic modifiers of tafazzin.
心磷脂（CL）是一种线粒体磷脂，有助于维持线粒体内膜的正常结构，并稳定电子传递链的蛋白质复合物，以促进高效的ATP合成。tafazzin是一种酰基转移酶，是合成成熟形式的CL所必需的。tafazzin（TAZ）基因突变与一种名为Barth综合征的人类疾病有关。Barth综合征的症状通常包括肌肉无力和运动不耐受。先前的研究表明，果蝇Taz突变体表现出运动无力，通过飞行和攀爬能力的降低来衡量。然而，果蝇TAZ突变体的基线耐力或对耐力运动训练的反应尚未得到评估。在这里，我们发现TAZ突变体的耐力降低，并且在典型的运动训练范式后没有改善，这表明TAZ功能的丧失导致果蝇运动不耐受。尽管在人类Barth综合征患者中观察到心脏表型，但TAZ突变体对心脏起搏具有正常的抵抗力。未来，耐力可能是一种有用的筛选工具，用于识别tafazzin的其他遗传修饰因子。
