Carbon monoxide shifts energetic metabolism from glycolysis to oxidative phosphorylation in endothelial cells.
Carbon monoxide (CO) modulates mitochondrial respiration, but the mechanisms involved are not completely understood. The aim of the present study was to investigate the acute effects of CO on bioenergetics and metabolism in intact EA.hy926 endothelial cells using live cell imaging techniques. Our findings indicate that CORM-401, a compound that liberates CO, reduces ATP production from glycolysis, and induces a mild mitochondrial depolarization. In addition, CO from CORM-401 increases mitochondrial calcium and activates complexes I and II. The subsequent increase in mitochondrial respiration leads to ATP production through oxidative phosphorylation. Thus, our results show that nonactivated endothelial cells rely primarily on glycolysis, but in the presence of CO, mitochondrial Ca2+increases and activates respiration that shifts the metabolism of endothelial cells from glycolysis- to oxidative phosphorylation-dependent ATP production.
Jagiellonian Centre for Experimental Therapeutics (JCET), Jagiellonian University, Krakow, Poland.
Patrycja
http://orcid.org/0000-0003-0106-4172
P
Kaczara
INSERM Unit 955, Equipe 12, Faculty of Medicine, University Paris-Est, Créteil, France.
Roberto
R
Motterlini
Jagiellonian Centre for Experimental Therapeutics (JCET), Jagiellonian University, Krakow, Poland.
Kamil
K
Kus
Jagiellonian Centre for Experimental Therapeutics (JCET), Jagiellonian University, Krakow, Poland.
Agnieszka
A
Zakrzewska
Department of Molecular Neuroscience, UCL Institute of Neurology, London, UK. a.abramov@ucl.ac.uk.
Andrey Y
AY
Abramov
Jagiellonian Centre for Experimental Therapeutics (JCET), Jagiellonian University, Krakow, Poland. stefan.chlopicki@jcet.eu.
Stefan
S
Chlopicki
D000255:Adenosine Triphosphate / Q000378:metabolism; D002118:Calcium / Q000378:metabolism; D002248:Carbon Monoxide / Q000378:metabolism*; D002460:Cell Line; D042967:Electron Transport Complex I / Q000187:drug effects; D042963:Electron Transport Complex II / Q000187:drug effects; D042783:Endothelial Cells / Q000378:metabolism*; D004734:Energy Metabolism / Q000187:drug effects*; D006019:Glycolysis / Q000187:drug effects; D006801:Humans; D008345:Manganese / Q000737:chemistry; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects; D008928:Mitochondria / Q000378:metabolism*; D009942:Organometallic Compounds / Q000737:chemistry / Q000494:pharmacology*; D010085:Oxidative Phosphorylation
D009942:Organometallic Compounds; D008345:Manganese; D002248:Carbon Monoxide; D000255:Adenosine Triphosphate; D042963:Electron Transport Complex II; D042967:Electron Transport Complex I; D002118:Calcium
CO-releasing molecule; carbon monoxide; endothelium; glycolysis; oxidative phosphorylation; respiration