Department of Biochemistry and Molecular Biology, Bio21 Molecular Science and Biotechnology Institute, University of Melbourne, Parkville 3052 Victoria, Australia.
Biochem Soc Trans. 2020 Apr 29;48(2):621-629. doi: 10.1042/BST20190930.
The four complexes of the mitochondrial respiratory chain are critical for ATP production in most eukaryotic cells. Structural characterisation of these complexes has been critical for understanding the mechanisms underpinning their function. The three proton-pumping complexes, Complexes I, III and IV associate to form stable supercomplexes or respirasomes, the most abundant form containing 80 subunits in mammals. Multiple functions have been proposed for the supercomplexes, including enhancing the diffusion of electron carriers, providing stability for the complexes and protection against reactive oxygen species. Although high-resolution structures for Complexes III and IV were determined by X-ray crystallography in the 1990s, the size of Complex I and the supercomplexes necessitated advances in sample preparation and the development of cryo-electron microscopy techniques. We now enjoy structures for these beautiful complexes isolated from multiple organisms and in multiple states and together they provide important insights into respiratory chain function and the role of the supercomplex. While we as non-structural biologists use these structures for interpreting our own functional data, we need to remind ourselves that they stand on the shoulders of a large body of previous structural studies, many of which are still appropriate for use in understanding our results. In this mini-review, we discuss the history of respiratory chain structural biology studies leading to the structures of the mammalian supercomplexes and beyond.
线粒体呼吸链的四个复合物对于大多数真核细胞中 ATP 的产生至关重要。这些复合物的结构特征对于理解其功能的机制至关重要。三个质子泵复合物，复合物 I、III 和 IV 结合形成稳定的超复合物或呼吸体，哺乳动物中最丰富的形式含有 80 个亚基。超复合物具有多种功能，包括增强电子载体的扩散、为复合物提供稳定性和防止活性氧的侵害。尽管复合物 III 和 IV 的高分辨率结构在 20 世纪 90 年代通过 X 射线晶体学确定，但复合物 I 和超复合物的大小需要在样品制备和低温电子显微镜技术的发展方面取得进展。现在我们拥有来自多种生物体和多种状态的这些美丽复合物的结构，它们共同为呼吸链功能和超复合物的作用提供了重要的见解。虽然我们作为非结构生物学家使用这些结构来解释我们自己的功能数据，但我们需要提醒自己，它们站在大量以前的结构研究的肩膀上，其中许多仍然适用于理解我们的结果。在这篇迷你综述中，我们讨论了导致哺乳动物超复合物结构以及其他结构产生的呼吸链结构生物学研究的历史。
