Mitochondrial respiration controls neoangiogenesis during wound healing and tumour growth.

Nature Communications
L M SchiffmannHamid Kashkar

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.

References

Apr 1, 1984·British Journal of Cancer·B Hobson, J Denekamp
Jan 6, 2000·Transgenic Research·B E ClausenI Förster
May 16, 2001·Genesis : the Journal of Genetics and Development·R ConstienB Arnold
Nov 16, 2002·Genesis : the Journal of Genetics and Development·Pantelis GeorgiadesCristin G Print
Mar 6, 2003·Neuroscience Letters·Christian RamakersAntoon F M Moorman
May 25, 2007·Nature Reviews. Molecular Cell Biology·Ralf H Adams, Kari Alitalo
Sep 18, 2007·Genesis : the Journal of Genetics and Development·Mandar Deepak MuzumdarLiqun Luo
Jul 5, 2008·Nature Protocols·Guillermo RepettoJorge L Zurita
Nov 27, 2008·The Journal of Clinical Investigation·Pierre SonveauxMark W Dewhirst
Feb 24, 2010·The Journal of Immunology : Official Journal of the American Association of Immunologists·Tina LucasSabine A Eming
Jul 21, 2010·Genesis : the Journal of Genetics and Development·Yuefeng TangLucy Liaw
Jan 18, 2011·Trends in Neurosciences·Igor AllamanPierre J Magistretti
Jul 9, 2011·Cell Death and Differentiation·L CabonS A Susin
May 25, 2012·Nature·Ursula FünfschillingKlaus-Armin Nave
Aug 6, 2013·Cell·Katrien De BockPeter Carmeliet
Sep 4, 2013·The Journal of Clinical Investigation·Joanne R Doherty, John L Cleveland
Sep 10, 2014·International Journal of Cancer. Journal International Du Cancer·Stefania OrecchioniFrancesco Bertolini
Mar 31, 2015·Circulation Research·Guy EelenPeter Carmeliet
Apr 2, 2015·Nature·Sandra SchoorsPeter Carmeliet
Feb 9, 2016·Cell·Christopher T HensleyRalph J DeBerardinis
Aug 5, 2016·Journal of the American Society of Nephrology : JASN·Anika KlingbergMatthias Gunzer
May 16, 2017·Nature Cell Biology·Elena AnsóNavdeep S Chandel
Jul 1, 2017·The EMBO Journal·Hongling HuangPeter Carmeliet
Jul 1, 2017·The EMBO Journal·Boa KimZoltan Arany
Jul 25, 2017·Trends in Cell Biology·Costas A Lyssiotis, Alec C Kimmelman
Sep 7, 2017·Angiogenesis·Lena-Christin ConradiPeter Carmeliet
Nov 21, 2017·Trends in Cell Biology·Katerina RohlenovaPeter Carmeliet
Nov 24, 2017·Physiological Reviews·Guy EelenPeter Carmeliet
Jul 19, 2018·Cell Metabolism·Saar VandekeerePeter Carmeliet
Nov 1, 2018·British Journal of Cancer·Lars Mortimer SchiffmannOliver Coutelle
May 21, 2019·Nature Metabolism·Lauren P DieboldNavdeep S Chandel

❮ Previous
Next ❯

Citations

Jun 2, 2021·Angiogenesis·Alessandra PasutPeter Carmeliet
Aug 14, 2021·Cell Metabolism·Sabine A EmingEdward J Pearce
Aug 19, 2021·Trends in Biotechnology·Matthias W Laschke, Michael D Menger

❮ Previous
Next ❯

Methods Mentioned

BETA
PCR
biopsies
genotyping
confocal microscopy
FCS
FACS
Protein Assay
Assay
profiler
flow cytometry

Software Mentioned

Cell R
TraceFinder
GraphPad Prism
Diskus
Excel
LinRegPCR
R
ImageJ
OxPhos

Related Concepts

Related Feeds

Cancer Metabolic Reprogramming (Keystone)

Cancer metabolic reprogramming is important for the rapid growth and proliferation of cancer cells. Cancer cells have the ability to change their metabolic demands depending on their environment, regulated by the activation of oncogenes or loss of tumor suppressor genes. Here is the latest research on cancer metabolic reprogramming.

Cancer Metabolic Reprogramming

Cancer metabolic reprogramming is important for the rapid growth and proliferation of cancer cells. Cancer cells have the ability to change their metabolic demands depending on their environment, regulated by the activation of oncogenes or loss of tumor suppressor genes. Here is the latest research on cancer metabolic reprogramming.