Letts James A, Fiedorczuk Karol, Degliesposti Gianluca, Skehel Mark, Sazanov Leonid A
Institute of Science and Technology Austria, Klosterneuberg 3400, Austria; Department of Molecular and Cellular Biology, University of California, Davis, Davis, CA 95616, USA.
Institute of Science and Technology Austria, Klosterneuberg 3400, Austria; Laboratory of Membrane Biophysics and Biology, The Rockefeller University, New York, NY 10065, USA.
Mol Cell. 2019 Sep 19;75(6):1131-1146.e6. doi: 10.1016/j.molcel.2019.07.022. Epub 2019 Sep 3.
The mitochondrial electron transport chain complexes are organized into supercomplexes (SCs) of defined stoichiometry, which have been proposed to regulate electron flux via substrate channeling. We demonstrate that CoQ trapping in the isolated SC I+III limits complex (C)I turnover, arguing against channeling. The SC structure, resolved at up to 3.8 Å in four distinct states, suggests that CoQ oxidation may be rate limiting because of unequal access of CoQ to the active sites of CIII. CI shows a transition between "closed" and "open" conformations, accompanied by the striking rotation of a key transmembrane helix. Furthermore, the state of CI affects the conformational flexibility within CIII, demonstrating crosstalk between the enzymes. CoQ was identified at only three of the four binding sites in CIII, suggesting that interaction with CI disrupts CIII symmetry in a functionally relevant manner. Together, these observations indicate a more nuanced functional role for the SCs.
线粒体电子传递链复合物被组织成具有特定化学计量的超复合物（SCs），有人提出这些超复合物通过底物通道化来调节电子通量。我们证明，在分离的SC I+III限制复合物（C）I周转中辅酶Q的捕获，这与通道化观点相悖。在四种不同状态下分辨率高达3.8 Å的SC结构表明，由于辅酶Q对CIII活性位点的不均等可及性，辅酶Q氧化可能是限速步骤。CI显示出“关闭”和“开放”构象之间的转变，伴随着一个关键跨膜螺旋的显著旋转。此外，CI的状态影响CIII内的构象灵活性，表明酶之间存在相互作用。在CIII的四个结合位点中仅在三个位点鉴定到辅酶Q，这表明与CI的相互作用以功能相关的方式破坏了CIII的对称性。总之，这些观察结果表明SCs具有更细微的功能作用。
