Mitochondrial complex III is necessary for endothelial cell proliferation during angiogenesis
Mitochondrial complex III is necessary for endothelial cell proliferation during angiogenesis
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DOI：
10.1038/s42255-018-0011-x
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发表时间：
2019-01-01
影响因子：
20.8
通讯作者：
Chandel, Navdeep S.
中科院分区：
文献类型：
--
作者：
Diebold, Lauren P.;Gil, Hyea Jin;Chandel, Navdeep S.
内皮细胞（EC）在血管生成过程中需要糖酵解来增殖和迁移；然而，血管生成过程中线粒体呼吸链的必要性尚不清楚。在此，我们报道抑制呼吸链复合物 III 通过降低 NAD(+)/NADH 比率来损害体外 EC 的增殖，但不会损害其迁移。为了确定线粒体呼吸是否是体内血管生成所必需的，我们有条件地消融了 EC 中呼吸链复合物 III (QPC) 的一个亚基。 QPC 的缺失会减少呼吸，导致 EC 增殖减少，并损害视网膜和肿瘤血管生成。 QPC 的缺失不会降低 EC 中与合成代谢相关的基因或核苷酸水平，但会降低氨基酸水平。我们的研究结果表明线粒体呼吸对于血管生成是必需的，并且线粒体在 EC 中的主要作用是作为细胞增殖的生物合成细胞器。
Endothelial cells (ECs) require glycolysis for proliferation and migration during angiogenesis; however, the necessity for the mitochondrial respiratory chain during angiogenesis is not known. Here we report that inhibition of respiratory chain complex III impairs proliferation, but not migration, of ECs in vitro by decreasing the NAD(+)/NADH ratio. To determine whether mitochondrial respiration is necessary for angiogenesis in vivo, we conditionally ablate a subunit of the respiratory chain complex III (QPC) in ECs. Loss of QPC decreases respiration, resulting in diminished EC proliferation, and impairment in retinal and tumour angiogenesis. Loss of QPC does not decrease genes associated with anabolism or nucleotide levels in ECs but diminishes amino acid levels. Our findings indicate that mitochondrial respiration is necessary for angiogenesis and that the primary role of mitochondria in ECs is to serve as biosynthetic organelles for cell proliferation.