Cardiolipin depletion–induced changes in the Trypanosoma brucei proteome

Schädeli, D., Serricchio, M., Ben Hamidane, H., Loffreda, A., Hemphill, A., Beneke, T., Gluenz, E. , Graumann, J. and Bütikofer, P. (2019) Cardiolipin depletion–induced changes in the Trypanosoma brucei proteome. FASEB Journal, 33(12), pp. 13161-13175. (doi: 10.1096/fj.201901184RR) (PMID:31536395)

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Abstract

The mitochondrial signature glycerophospholipid, cardiolipin (CL), binds to transporters of the inner mitochondrial membrane and plays a central role in formation and stability of respiratory supercomplexes. Functional and structural requirement of CL for mitochondrial membrane proteins has been studied in vitro using purified reconstituted proteins or in CL synthesis knockout cells that are viable under specific growth conditions. However, no information is available on mitochondrial function, protein stability, or expression levels in cells during CL depletion. In contrast to yeast and mammalian cells, CL synthesis is essential in Trypanosoma brucei. By stable isotope labeling with amino acids in cell culture and mass spectrometry, we analyzed protein levels in T. brucei procyclic forms at different time points during depletion of CL using tightly controllable conditional CL synthase knockout mutants and identified a set of novel CL-dependent proteins (CLDPs) with unknown functions. Depletion of individual CLDPs using knockout or knockdown technologies showed that although CL synthesis is essential, expression of a given CLDP is not. In addition, ablation of CL synthesis leads to respiratory supercomplex instability and altered mitochondrial ultrastructure and function. Our findings suggest that CL may bind to and affect many more proteins in eukaryotes than previously thought.—Schädeli, D., Serricchio, M., Ben Hamidane, H., Loffreda, A., Hemphill, A., Beneke, T., Gluenz, E., Graumann, J., Bütikofer, P. Cardiolipin depletion–induced changes in the Trypanosoma brucei proteome.

Item Type:Articles
Additional Information:This work was supported by Swiss National Science Foundation Grants 149353 and 169355 (to P.B.).
Status:Published
Refereed:Yes
Glasgow Author(s) Enlighten ID:Gluenz, Dr Eva
Authors: Schädeli, D., Serricchio, M., Ben Hamidane, H., Loffreda, A., Hemphill, A., Beneke, T., Gluenz, E., Graumann, J., and Bütikofer, P.
College/School:College of Medical Veterinary and Life Sciences > Institute of Infection Immunity and Inflammation
Journal Name:FASEB Journal
Publisher:Federation of American Society of Experimental Biology
ISSN:0892-6638
ISSN (Online):1530-6860
Published Online:19 September 2019

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