Supporting Aspartate Biosynthesis Is an Essential Function of Respiration in Proliferating Cells.
Supporting Aspartate Biosynthesis Is an Essential Function of Respiration in Proliferating Cells.
复制标题
DOI：
10.1016/j.cell.2015.07.017
复制
发表时间：
2015-07-30
期刊：
影响因子：
64.5
通讯作者：
Vander Heiden MG
中科院分区：
文献类型：
--
作者：
Sullivan LB;Gui DY;Hosios AM;Bush LN;Freinkman E;Vander Heiden MG
线粒体呼吸对于细胞增殖是重要的，然而通过呼吸来支持增殖的特定代谢要求尚未被定义。在这里，我们表明，呼吸在增殖细胞中的一个主要作用是提供电子受体天冬氨酸合成。这一发现与缺乏功能性呼吸链的细胞是丙酮酸营养缺陷型的观察结果一致，丙酮酸是一种外源性电子受体。此外，丙酮酸的需求可以用另一种电子受体α-酮丁酸来满足，它既不为细胞提供碳也不提供ATP。当呼吸被抑制时，α-酮丁酸盐恢复增殖，这表明替代电子受体可以代替呼吸来支持增殖。我们发现，电子受体是限制生产天冬氨酸，并提供天冬氨酸使呼吸缺陷细胞增殖的情况下，外源性电子受体。总之，这些数据表明增殖细胞中呼吸的主要功能是支持天冬氨酸合成。
Mitochondrial respiration is important for cell proliferation, however the specific metabolic requirements fulfilled by respiration to support proliferation have not been defined. Here we show that a major role of respiration in proliferating cells is to provide electron acceptors for aspartate synthesis. This finding is consistent with the observation that cells lacking a functional respiratory chain are auxotrophic for pyruvate, which serves as an exogenous electron acceptor. Further, the pyruvate requirement can be fulfilled with an alternative electron acceptor, alpha-ketobutyrate, which provides cells neither carbon nor ATP. Alpha-ketobutyrate restores proliferation when respiration is inhibited, suggesting that an alternative electron acceptor can substitute for respiration to support proliferation. We find that electron acceptors are limiting for producing aspartate, and supplying aspartate enables proliferation of respiration deficient cells in the absence of exogenous electron acceptors. Together, these data argue a major function of respiration in proliferating cells is to support aspartate synthesis.