Mitochondrial complex III is necessary for endothelial cell proliferation during angiogenesis

Area of Science:

• Cellular biology
• Mitochondrial function
• Angiogenesis research

Background:

• Endothelial cells (ECs) rely on glycolysis for proliferation and migration in angiogenesis.
• The role of the mitochondrial respiratory chain in angiogenesis remains unclear.

Purpose of the Study:

• To investigate the necessity of the mitochondrial respiratory chain for angiogenesis.
• To determine the specific functions of mitochondria in endothelial cells during angiogenesis.

Main Methods:

• Inhibition of respiratory chain complex III in ECs in vitro.
• Conditional ablation of a respiratory chain complex III subunit (QPC) in ECs in vivo.
• Analysis of EC proliferation, migration, NAD+/NADH ratio, gene expression, and metabolite levels.

Main Results:

• Inhibition of respiratory chain complex III impaired EC proliferation but not migration in vitro by decreasing the NAD+/NADH ratio.
• Conditional ablation of QPC in ECs reduced respiration, EC proliferation, and both retinal and tumor angiogenesis.
• Loss of QPC diminished amino acid levels in ECs without affecting anabolism or nucleotide levels.

Conclusions:

• Mitochondrial respiration is indispensable for angiogenesis.
• Mitochondria in ECs primarily function as biosynthetic organelles supporting cell proliferation.
• The NAD+/NADH ratio and amino acid synthesis are critical downstream effectors of mitochondrial respiration in angiogenesis.