Mitochondrial respiration controls neoangiogenesis during wound healing and tumour growth

L. M. Schiffmann, J. P. Werthenbach, F. Heintges-Kleinhofer, J. M. Seeger, M. Fritsch, S. D. Günther, S. Willenborg, S. Brodesser, C. Lucas, C. Jüngst, M. C. Albert, F. Schorn, A. Witt, C. T. Moraes, C. J. Bruns, M. Pasparakis, M. Krönke, S. A. Eming, O. Coutelle, H. Kashkar

Research output: Contribution to journalArticlepeer-review

Abstract

The vasculature represents a highly plastic compartment, capable of switching from a quiescent to an active proliferative state during angiogenesis. Metabolic reprogramming in endothelial cells (ECs) thereby is crucial to cover the increasing cellular energy demand under growth conditions. Here we assess the impact of mitochondrial bioenergetics on neovascularisation, by deleting cox10 gene encoding an assembly factor of cytochrome c oxidase (COX) specifically in mouse ECs, providing a model for vasculature-restricted respiratory deficiency. We show that EC-specific cox10 ablation results in deficient vascular development causing embryonic lethality. In adult mice induction of EC-specific cox10 gene deletion produces no overt phenotype. However, the angiogenic capacity of COX-deficient ECs is severely compromised under energetically demanding conditions, as revealed by significantly delayed wound-healing and impaired tumour growth. We provide genetic evidence for a requirement of mitochondrial respiration in vascular endothelial cells for neoangiogenesis during development, tissue repair and cancer.

Original languageEnglish (US)
Article number3653
JournalNature communications
Volume11
Issue number1
DOIs
StatePublished - Dec 1 2020

ASJC Scopus subject areas

  • Chemistry(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Physics and Astronomy(all)

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