Loffreda, Alessio; Schlame, Michael; Bütikofer, Peter (2022). StaR-related lipid transfer-like domain-containing protein CLDP43 affects cardiolipin synthesis and mitochondrial function in Trypanosoma brucei. PLoS ONE, 17(4), e0259752. Public Library of Science 10.1371/journal.pone.0259752
|
Text
journal.pone.0259752.pdf - Published Version Available under License Creative Commons: Attribution (CC-BY). Download (2MB) | Preview |
Cardiolipin is known to interact with bacterial and mitochondrial proteins and protein complexes. Unlike in Escherichia coli and Saccharomyces cerevisiae, the synthesis of cardiolipin is essential for growth of Trypanosoma brucei parasites in culture. Inhibition of cardiolipin production has been shown to result in major changes in the T. brucei proteome and energy metabolism, with CLDP43, a mitochondrial protein containing a StaR-related lipid transfer (START)-like domain, being depleted in a cardiolipin-dependent way. We now show that in T. brucei procyclic forms lacking CLDP43, cardiolipin metabolism and mitochondrial function are affected. Using quantitative and qualitative lipid analyses, we found that while steady-state levels of cardiolipin were elevated in CLDP43 knock-out parasites compared to parental cells, de novo formation of cardiolipin was down-regulated. In addition, depletion of CLDP43 resulted in partial loss of mitochondrial membrane potential and decreased ATP production via substrate level phosphorylation. Recombinant CLDP43 was found to bind cardiolipin and phosphatidic acid in lipid overlay experiments, suggesting that it may be involved in transport or synthesis of cardiolipin or its precursors in T. brucei.
Item Type: |
Journal Article (Original Article) |
|---|---|
Division/Institute: |
04 Faculty of Medicine > Pre-clinic Human Medicine > Institute of Biochemistry and Molecular Medicine |
Graduate School: |
Graduate School for Cellular and Biomedical Sciences (GCB) |
UniBE Contributor: |
Loffreda, Alessio, Bütikofer, Peter |
Subjects: |
500 Science > 570 Life sciences; biology 600 Technology > 610 Medicine & health |
ISSN: |
1932-6203 |
Publisher: |
Public Library of Science |
Language: |
English |
Submitter: |
Pubmed Import |
Date Deposited: |
26 Apr 2022 11:41 |
Last Modified: |
05 Dec 2022 16:19 |
Publisher DOI: |
10.1371/journal.pone.0259752 |
PubMed ID: |
35452450 |
BORIS DOI: |
10.48350/169462 |
URI: |
https://boris.unibe.ch/id/eprint/169462 |
Actions (login required)
 |
Edit item |