Department of Cellular Biology, University of Georgia , Athens, Georgia, USA.
Center for Tropical and Emerging Global Diseases, University of Georgia , Athens, Georgia, USA.
mBio. 2023 Oct 31;14(5):e0176923. doi: 10.1128/mbio.01769-23. Epub 2023 Oct 5.
Members of the coiled-coil-helix-coiled-coil-helix (CHCH) domain protein family are transported into the mitochondrial intermembrane space, where they play important roles in the biogenesis and function of the organelle. Unexpectedly, the ATP synthase of the apicomplexan harbors CHCH domain-containing subunits of unknown function. As no other ATP synthase studied to date contains this class of proteins, characterizing their function will be of broad interest to the fields of molecular parasitology and mitochondrial evolution. Here, we demonstrate that that two ATP synthase subunits containing CHCH domains are required for parasite survival and for stability and function of the ATP synthase. We also show that knockdown disrupts multiple aspects of the mitochondrial morphology of and that mutation of key residues in the CHCH domains caused mis-localization of the proteins. This work provides insight into the unique features of the apicomplexan ATP synthase, which could help to develop therapeutic interventions against this parasite and other apicomplexans, such as the malaria-causing parasite .
卷曲螺旋-环-卷曲螺旋-环（CHCH）结构域蛋白家族的成员被运送到线粒体的膜间空间，在那里它们在细胞器的生物发生和功能中发挥着重要作用。出人意料的是，锥体虫的 ATP 合酶含有具有未知功能的 CHCH 结构域的亚基。由于迄今为止研究过的其他 ATP 合酶都不含有这类蛋白质，因此它们的功能将引起分子寄生虫学和线粒体进化领域的广泛关注。在这里，我们证明含有 CHCH 结构域的两个 ATP 合酶亚基对于寄生虫的存活以及对于 ATP 合酶的稳定性和功能是必需的。我们还表明，敲低会破坏 的线粒体形态的多个方面，并且 CHCH 结构域中的关键残基的突变导致蛋白质的定位错误。这项工作深入了解了锥体虫 ATP 合酶的独特特征，这可能有助于针对这种寄生虫和其他锥体虫（如引起疟疾的寄生虫 ）开发治疗干预措施。
