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Roshan Jha

Shuo Liang

 

The role of structural lipids in proton translocation of respiratory complexes

Principal investigator: Prof. Dr. Carola Hunte

Institut für Biochemie und Molekularbiologie
Stefan-Meier-Str. 19
79104 Freiburg

Phone: +49 (0) 761-203-5277
roshan.jha@biochemie.uni-freiburg.de

 

Abstract

Membrane lipids provide both structural and functional integrity to membrane proteins [1]. Cardiolipin, a mitochondrial phospholipid, is essential for the optimal functioning of the mitochondrial OXPHOS system [2]. Presence of distinct cardioliopin binding site has been described in structure of Cytochrome bc1 complex [3, 4] and delipidation inactivates Cytochorme bc1 complex and alters the formation of Supercomplexes. The molecular mechanism underlying the structure-function relationship between cardiolipin and Cytochrome bc1 complex is still not well understood. The importance of cardiolipin is further underscored by Barth syndrome, a cardio-skeletal myopathy due to defective activity of tafazzin enzyme [5]. Cardiolipin biosynthesis has been extensively studied in yeast. This makes yeast as the best and the only available model to study the role of cardiolipin in mitochondrial respiratory functions.

The present study will focus on the role of cardiolipin in Cyt bc1 complex through structural characterization of Cyt bc1complex from yeast strains carrying deletion of specific genes involved in cardiolipin synthesis and remodeling.

Methods

Membrane protein purification, Enzyme assay, LC-MS based lipid profiling, X-ray crystallography

References

  1. Hunte, C. and S. Richers, Lipids and membrane protein structures. Curr Opin Struct Biol, 2008. 18(4): p. 406-11.
  2. Jiang, F., et al., Absence of Cardiolipin in the crd1 Null Mutant Results in Decreased Mitochondrial Membrane Potential and Reduced Mitochondrial Function. Journal of Biological Chemistry, 2000. 275(29): p. 22387-22394.
  3. Lange, C., et al., Specific roles of protein-phospholipid interactions in the yeast cytochrome bc1 complex structure.The EMBO Journal, 2001. 20(23): p. 6591-6600.
  4. Wenz, T., et al., Role of phospholipids in respiratory cytochrome bc(1) complex catalysis and supercomplex formation.Biochim Biophys Acta, 2009. 1787(6): p. 609-16.
  5. Ren, M., C.K.L. Phoon, and M. Schlame, Metabolism and function of mitochondrial cardiolipin. Progress in Lipid Research, 2014. 55: p. 1-16.