The consequence of ATP synthase dimer angle on mitochondrial morphology studied by cryo-electron tomography
The consequence of ATP synthase dimer angle on mitochondrial morphology studied by cryo-electron tomography
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低温电子断层扫描研究 ATP 合酶二聚体角度对线粒体形态的影响
DOI：
10.1101/2023.02.02.526626
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发表时间：
2023
期刊：
影响因子：
--
通讯作者：
Buzzard E
中科院分区：
文献类型：
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作者：
Buzzard E
线粒体 ATP 合酶形成一排二聚体，诱导膜弯曲，使嵴具有特征性的层状或管状形态。 ATP 合酶二聚体中心茎之间形成的角度因物种而异。使用冷冻电子断层扫描和亚断层扫描平均，我们确定了线虫秀丽隐杆线虫的 ATP 合酶二聚体的结构，并表明二聚体角度与之前确定的结构不同。通过比较秀丽隐杆线虫和酿酒酵母线粒体形态，研究了二聚体界面上这种物种特异性差异的后果。我们发现，与酵母相比，线虫具有更大的 ATP 合酶二聚体角度和更多的层状（更平坦）嵴。通过同源建模生成线虫 ATP 合酶二聚体的原子模型，研究了这种差异的根本原因。我们的线虫模型与现有的酿酒酵母结构的比较揭示了线虫亚基中存在与维持二聚体界面相关的延伸和重排。我们推测，增加二聚体角度可以通过形成更平坦、更高效的嵴，为栖息于可变氧环境的物种提供优势。
Mitochondrial ATP synthases form rows of dimers, which induce membrane curvature to give cristae their characteristic lamellar or tubular morphology. The angle formed between the central stalks of ATP synthase dimers varies between species. Using cryo-electron tomography and sub-tomogram averaging, we determined the structure of the ATP synthase dimer from the nematode worm Caenorhabditis elegans and show that the dimer angle differs from previously determined structures. The consequences of this speciesspecific difference at the dimer interface were investigated by comparing C. elegans and Saccharomyces cerevisiae mitochondrial morphology. We reveal that C. elegans has a larger ATP synthase dimer angle with more lamellar (flatter) cristae when compared with yeast. The underlying cause of this difference was investigated by generating an atomic model of the C. elegans ATP synthase dimer by homology modelling. A comparison of our C. elegans model to an existing S. cerevisiae structure reveals the presence of extensions and rearrangements in C. elegans subunits associated with maintaining the dimer interface. We speculate that increasing dimer angles could provide an advantage for species that inhabit variable-oxygen environments by forming flatter, more energetically efficient cristae.