近日，美国麻省理工学院Jessica B. Spinelli等研究人员发现，富马酸是哺乳动物电子传递链中的终端电子受体。相关论文于2021年12月2日发表在《科学》杂志上。

要使电子持续进入并流经线粒体电子传输链（ETC），它们最终必须落在终端电子受体（TEA）上，已知在哺乳动物中这是氧气。矛盾的是，研究人员发现当氧还原受阻时，复合物I和二氢乳酸脱氢酶（DHODH）仍能将电子存入ETC。缺乏氧还原的细胞积累泛醌，反向驱动琥珀酸脱氢酶（SDH）复合物，使电子沉积到富马酸上。当氧还原受到抑制时，富马酸盐的还原维持了DHODH和复合体I的活动。

小鼠组织显示出不同的使用富马酸盐作为TEA的能力，其中大部分在缺氧情况下净逆转SDH复合物。因此，研究人员在哺乳动物ETC中划定了一个电子流回路，在氧限制下维持线粒体功能。

附：英文原文

Title: Fumarate is a terminal electron acceptor in the mammalian electron transport chain

Author: Jessica B. Spinelli, Paul C. Rosen, Hans-Georg Sprenger, Anna M. Puszynska, Jessica L. Mann, Julian M. Roessler, Andrew L. Cangelosi, Antonia Henne, Kendall J. Condon, Tong Zhang, Tenzin Kunchok, Caroline A. Lewis, Navdeep S. Chandel, David M. Sabatini

Issue&Volume: 2021-12-03

Abstract: 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.

DOI: abi7495

Source: https://www.science.org/doi/10.1126/science.abi7495