Whitehead Institute for Biomedical Research, Cambridge, MA 02142, USA.
Howard Hughes Medical Institute, Department of Biology, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.
Science. 2021 Dec 3;374(6572):1227-1237. doi: 10.1126/science.abi7495. Epub 2021 Dec 2.
For electrons to continuously enter and flow through the mitochondrial electron transport chain (ETC), they must ultimately land on a terminal electron acceptor (TEA), which is known to be oxygen in mammals. Paradoxically, we find that complex I and dihydroorotate dehydrogenase (DHODH) can still deposit electrons into the ETC when oxygen reduction is impeded. Cells lacking oxygen reduction accumulate ubiquinol, driving the succinate dehydrogenase (SDH) complex in reverse to enable electron deposition onto fumarate. Upon inhibition of oxygen reduction, fumarate reduction sustains DHODH and complex I activities. Mouse tissues display varying capacities to use fumarate as a TEA, most of which net reverse the SDH complex under hypoxia. Thus, we delineate a circuit of electron flow in the mammalian ETC that maintains mitochondrial functions under oxygen limitation.
为了让电子持续进入并流经线粒体电子传递链（ETC），它们最终必须落在末端电子受体（TEA）上，已知哺乳动物中的 TEA 是氧气。矛盾的是，我们发现当氧还原受到阻碍时，复合物 I 和二氢乳清酸脱氢酶（DHODH）仍然可以将电子沉积到 ETC 中。缺乏氧还原的细胞积累泛醌，驱动琥珀酸脱氢酶（SDH）复合物反向运转，从而使电子沉积到延胡索酸上。当氧还原受到抑制时，延胡索酸还原维持 DHODH 和复合物 I 的活性。小鼠组织显示出利用延胡索酸作为 TEA 的不同能力，其中大多数在缺氧下净反向 SDH 复合物。因此，我们描绘了哺乳动物 ETC 中的电子流循环，该循环在氧气限制下维持线粒体功能。
