GSE121770
Endothelial-specific mitochondiral complex III KO leads to lung endothelial cell gene deregulation.
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 tumor angiogenesis.  Loss of QPC does not decrease genes associated with anabolism or nucleotides 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. Overall design: We conditionally knocked out a subunit of mitochondrial complex III (QPC) in Endothelial cells. KO was initiated via tamoxifen treatment on P0. Lungs were collected from WT and KO P15 mice and endothelial cells were isolated by positively sorting for CD31+ cells via FACS.