Imperial College London
Portrait Picture

Professor Beata Wojciak-Stothard

Faculty of Medicine, National Heart & Lung Institute

Professor in Vascular Biology
 
 
 
//

Contact

 

+44 (0)20 7594 6821b.wojciak-stothard

 
 
//

Location

 

535ICTEM buildingHammersmith Campus

//

Summary

 

Publications

Citation

BibTex format

@article{Alzaydi:2023:10.1165/rcmb.2022-0111OC,
author = {Alzaydi, M and Abdul, Salam V and Whitwell, H and Russomanno, G and Glynos, A and Capece, D and Szabadkai, G and Wilkins, M and Wojciak, Stothard B and Wojciak-Stothard, B},
doi = {10.1165/rcmb.2022-0111OC},
journal = {American Journal of Respiratory Cell and Molecular Biology},
pages = {103--115},
title = {Intracellular chloride channels regulate endothelial metabolic reprogramming in pulmonary arterial hypertension},
url = {http://dx.doi.org/10.1165/rcmb.2022-0111OC},
volume = {63},
year = {2023}
}
Download

RIS format (EndNote, RefMan)

TY  - JOUR
AB  - Mitochondrial fission and a metabolic switch from oxidative phosphorylation to glycolysis are key features of vascular pathology in pulmonary arterial hypertension (PAH) and are associated with exuberant endothelial proliferation and apoptosis. The underlying mechanisms are poorly understood. We describe the contribution of two intracellular chloride channel proteins CLIC1 and CLIC4, both highly expressed in PAH and cancer, to mitochondrial dysfunction and energy metabolism in PAH endothelium. Pathological overexpression of CLIC proteins induces mitochondrial fragmentation, inhibits mitochondrial cristae formation and induces metabolic shift towards glycolysis in human pulmonary artery endothelial cells, consistent with changes observed in patient-derived cells. Interactions of CLIC proteins with structural components of the inner mitochondrial membrane offer mechanistic insights. Endothelial CLIC4 excision and mitofusin 2 supplementation have protective effects in human PAH cells and pre-clinical PAH. This study is first to demonstrate the key role of endothelial intracellular chloride channels in the regulation of mitochondrial structure, biogenesis, and metabolic reprogramming in expression of the PAH phenotype.
AU  - Alzaydi,M
AU  - Abdul,Salam V
AU  - Whitwell,H
AU  - Russomanno,G
AU  - Glynos,A
AU  - Capece,D
AU  - Szabadkai,G
AU  - Wilkins,M
AU  - Wojciak,Stothard B
AU  - Wojciak-Stothard,B
DO  - 10.1165/rcmb.2022-0111OC
EP  - 115
PY  - 2023///
SN  - 1044-1549
SP  - 103
TI  - Intracellular chloride channels regulate endothelial metabolic reprogramming in pulmonary arterial hypertension
T2  - American Journal of Respiratory Cell and Molecular Biology
UR  - http://dx.doi.org/10.1165/rcmb.2022-0111OC
UR  - http://hdl.handle.net/10044/1/99808
VL  - 63
ER  -
Download