The Library
Cardiolipin, and not monolysocardiolipin, preferentially binds to the interface of complexes III and IV
Tools
Corey, Robin A., Harrison, Noah, Stansfeld, Phillip J., Sansom, Mark S. P. and Duncan, Anna L. (2022) Cardiolipin, and not monolysocardiolipin, preferentially binds to the interface of complexes III and IV. Chemical Science, 13 (45). pp. 13489-13498. doi:10.1039/d2sc04072g ISSN 2041-6520.
|
PDF
WRAP-Cardiolipin-not-monolysocardiolipin-binds-interface-complexes-III-IV-22.pdf - Published Version - Requires a PDF viewer. Available under License Creative Commons Attribution. Download (869Kb) | Preview |
Official URL: http://dx.doi.org/10.1039/d2sc04072g
Abstract
The mitochondrial electron transport chain comprises a series of protein complexes embedded in the inner mitochondrial membrane that generate a proton motive force via oxidative phosphorylation, ultimately generating ATP. These protein complexes can oligomerize to form larger structures called supercomplexes. Cardiolipin (CL), a conical lipid, unique within eukaryotes to the inner mitochondrial membrane, has proven essential in maintaining the stability and function of supercomplexes. Monolysocardiolipin (MLCL) is a CL variant that accumulates in people with Barth syndrome (BTHS). BTHS is caused by defects in CL biosynthesis and characterised by abnormal mitochondrial bioenergetics and destabilised supercomplexes. However, the mechanisms by which MLCL causes pathogenesis remain unclear. Here, multiscale molecular dynamics characterise the interactions of CL and MLCL with yeast and mammalian mitochondrial supercomplexes containing complex III (CIII) and complex IV (CIV). Coarse-grained simulations reveal that both CL and MLCL bind to sites at the interface between CIII and CIV of the supercomplex. Free energy perturbation calculations show that MLCL interaction is weaker than that of CL and suggest that interaction with CIV drives this difference. Atomistic contact analyses show that, although interaction with CIII is similar for CL and MLCL, CIV makes more contacts with CL than MLCL, demonstrating that CL is a more successful “glue” between the two complexes. Simulations of the human CIII2CIV supercomplex show that this interface site is maintained between species. Our study suggests that MLCL accumulation in people with BTHS disrupts supercomplex stability by formation of relatively weak interactions at the interface lipid binding site.
Item Type: | Journal Article | |||||||||||||||||||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
Subjects: | Q Science > QD Chemistry Q Science > QH Natural history Q Science > QP Physiology Q Science > QR Microbiology |
|||||||||||||||||||||||||||
Divisions: | Faculty of Science, Engineering and Medicine > Science > Life Sciences (2010- ) | |||||||||||||||||||||||||||
Library of Congress Subject Headings (LCSH): | Cardiolipin , Mitochondria , Phosphorylation , Adenosine triphosphate, Membrane proteins | |||||||||||||||||||||||||||
Journal or Publication Title: | Chemical Science | |||||||||||||||||||||||||||
Publisher: | Royal Society of Chemistry | |||||||||||||||||||||||||||
ISSN: | 2041-6520 | |||||||||||||||||||||||||||
Official Date: | 7 December 2022 | |||||||||||||||||||||||||||
Dates: |
|
|||||||||||||||||||||||||||
Volume: | 13 | |||||||||||||||||||||||||||
Number: | 45 | |||||||||||||||||||||||||||
Page Range: | pp. 13489-13498 | |||||||||||||||||||||||||||
DOI: | 10.1039/d2sc04072g | |||||||||||||||||||||||||||
Status: | Peer Reviewed | |||||||||||||||||||||||||||
Publication Status: | Published | |||||||||||||||||||||||||||
Access rights to Published version: | Open Access (Creative Commons) | |||||||||||||||||||||||||||
Date of first compliant deposit: | 19 December 2022 | |||||||||||||||||||||||||||
Date of first compliant Open Access: | 19 December 2022 | |||||||||||||||||||||||||||
RIOXX Funder/Project Grant: |
|
Request changes or add full text files to a record
Repository staff actions (login required)
View Item |
Downloads
Downloads per month over past year