An essential bacterial-type cardiolipin synthase mediates cardiolipin formation in a eukaryote

Serricchio, Mauro; Bütikofer, Peter (2012). An essential bacterial-type cardiolipin synthase mediates cardiolipin formation in a eukaryote. Proceedings of the National Academy of Sciences of the United States of America - PNAS, 109(16), E954-61. Washington, D.C.: National Academy of Sciences NAS 10.1073/pnas.1121528109

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Cardiolipin is important for bacterial and mitochondrial stability and function. The final step in cardiolipin biosynthesis is catalyzed by cardiolipin synthase and differs mechanistically between prokaryotes and eukaryotes. To study the importance of cardiolipin synthesis for mitochondrial integrity, membrane protein complex formation, and cell proliferation in the human and animal pathogenic protozoan parasite, Trypanosoma brucei, we generated conditional cardiolipin synthase-knockout parasites. We found that cardiolipin formation in T. brucei procyclic forms is catalyzed by a bacterial-type cardiolipin synthase, providing experimental evidence for a prokaryotic-type cardiolipin synthase in a eukaryotic organism. Ablation of enzyme expression resulted in inhibition of de novo cardiolipin synthesis, reduction in cellular cardiolipin levels, alterations in mitochondrial morphology and function, and parasite death in culture. By using immunofluorescence microscopy and blue-native gel electrophoresis, cardiolipin synthase was shown to colocalize with inner mitochondrial membrane proteins and to be part of a large protein complex. During depletion of cardiolipin synthase, the levels of cytochrome oxidase subunit IV and cytochrome c1, reflecting mitochondrial respiratory complexes IV and III, respectively, decreased progressively.

Item Type:

Journal Article (Original Article)

Division/Institute:

04 Faculty of Medicine > Pre-clinic Human Medicine > Institute of Biochemistry and Molecular Medicine

UniBE Contributor:

Serricchio, Mauro and Bütikofer, Peter

ISSN:

0027-8424

Publisher:

National Academy of Sciences NAS

Language:

English

Submitter:

Factscience Import

Date Deposited:

04 Oct 2013 14:37

Last Modified:

06 Dec 2013 13:37

Publisher DOI:

10.1073/pnas.1121528109

PubMed ID:

22451910

Web of Science ID:

000303246100007

URI:

https://boris.unibe.ch/id/eprint/15036 (FactScience: 222190)

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