Acute Severe Hypoxia Decreases Mitochondrial Chain Complex II Respiration in Human Peripheral Blood Mononuclear Cells.

Fiche publication

Date publication

janvier 2025

Journal

International journal of molecular sciences

Auteurs

Membres identifiés du Cancéropôle Est :
Pr GENY Bernard

Tous les auteurs :
Riou M, Charles AL, Enache I, Evrard C, Pistea C, Giannini M, Charloux A, Geny B

Lien Pubmed

https://www.ncbi.nlm.nih.gov/pubmed/39859418

Résumé

Peripheral blood mononuclear cells' (PBMCs) mitochondrial respiration is impaired and likely involved in myocardial injury and heart failure pathophysiology, but its response to acute and severe hypoxia, often associated with such diseases, is largely unknown in humans. We therefore determined the effects of acute hypoxia on PBMC mitochondrial respiration and ROS production in healthy volunteers exposed to controlled oxygen reduction, achieving an inspired oxygen fraction of 10.5%. We also investigated potential relationships with gene expression of key biomarkers of hypoxia, succinate and inflammation, as hypoxia and inflammation share common mechanisms involved in cardiovascular disease. Unlike global mitochondrial respiration, hypoxemia with a spO ≤ 80% significantly reduced PBMC complex II respiration (from 6.5 ± 1.2 to 3.1 ± 0.5 pmol/s/10 cell, = 0.04). Complex II activity correlated positively with spO (r = 0.63, = 0.02) and inversely correlated with the succinate receptor SUCNR1 (r = -0.68), the alpha-subunit of the hypoxia-inducible factor (HIF-1α, r = -0.61), the chemokine ligand-9 (r = -0.68) and interferon-stimulated gene 15 (r = -0.75). In conclusion, severe hypoxia specifically impairs complex II respiration in association with succinate, inflammation and HIF-1α pathway interactions in human PBMCs. These results support further studies investigating whether modulation of complex II activity might modify the inflammatory and metabolic alterations observed in heart failure.