Department of Physiology, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
Sci Adv. 2020 Aug 28;6(35):eabb0780. doi: 10.1126/sciadv.abb0780. eCollection 2020 Aug.
The phospholipid cardiolipin has pleiotropic structural and functional roles that are collectively essential for mitochondrial biology. Yet, the molecular details of how this lipid supports the structure and function of proteins and protein complexes are poorly understood. To address this property of cardiolipin, we use the mitochondrial adenosine 5'-diphosphate/adenosine 5'-triphosphate carrier (Aac) as a model. Here, we have determined that cardiolipin is critical for both the tertiary and quaternary assembly of the major yeast Aac isoform Aac2 as well as its conformation. Notably, these cardiolipin-provided structural roles are separable. In addition, we show that multiple copies of Aac2 engage in shared complexes that are largely dependent on the presence of assembled respiratory complexes III and IV or respiratory supercomplexes. Intriguingly, the assembly state of Aac2 is sensitive to its transport-related conformation. Together, these results expand our understanding of the numerous structural roles provided by cardiolipin for mitochondrial membrane proteins.
磷脂心磷脂具有多种结构和功能作用，这些作用对于线粒体生物学都是必不可少的。然而，人们对于这种脂质如何支持蛋白质和蛋白质复合物的结构和功能的分子细节知之甚少。为了解决心磷脂的这一特性，我们以线粒体腺苷 5′-二磷酸/腺苷 5′-三磷酸载体（Aac）为模型。在这里，我们已经确定心磷脂对于主要酵母 Aac 同工型 Aac2 的三级和四级组装及其构象都是至关重要的。值得注意的是，这些心磷脂提供的结构作用是可分离的。此外，我们还表明，多个 Aac2 拷贝参与共享复合物，这些复合物在很大程度上依赖于已组装的呼吸复合物 III 和 IV 或呼吸超级复合物的存在。有趣的是，Aac2 的组装状态对其运输相关构象敏感。总之，这些结果扩展了我们对心磷脂为线粒体膜蛋白提供的众多结构作用的理解。
