Open AccessStaR-related lipid transfer-like domain-containing protein CLDP43 affects cardiolipin synthesis and mitochondrial function in Trypanosoma brucei
Author(s) -
Alessio Loffreda,
Michael Schlame,
Peter Bütikofer
Publication year - 2022
Publication title -
plos one
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.99
H-Index - 332
ISSN - 1932-6203
DOI - 10.1371/journal.pone.0259752
Subject(s) - cardiolipin , trypanosoma brucei , biology , biochemistry , saccharomyces cerevisiae , cardiolipins , mitochondrion , inner mitochondrial membrane , microbiology and biotechnology , phospholipid , yeast , membrane , gene
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 .