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Publication : Mitochondrial respiration controls neoangiogenesis during wound healing and tumour growth.

First Author  Schiffmann LM Year  2020
Journal  Nat Commun Volume  11
Issue  1 Pages  3653
PubMed ID  32694534 Mgi Jnum  J:292228
Mgi Id  MGI:6447168 Doi  10.1038/s41467-020-17472-2
Citation  Schiffmann LM, et al. (2020) Mitochondrial respiration controls neoangiogenesis during wound healing and tumour growth. Nat Commun 11(1):3653
abstractText  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.
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