A component of the mitochondrial outer membrane proteome of T. brucei probably contains covalent bound fatty acids

Abstract

ABSTRACT:A subclass of eukaryotic proteins is subject to modification with fatty acids, the most common of which are palmitic and myristic acid. Protein acylation allows association with cellular membranes in the absence of transmembrane domains. Here we examine POMP39, a protein previously described to be present in the outer mitochondrial membrane proteome (POMP) of the protozoan parasite Trypanosoma brucei. POMP39 lacks canonical transmembrane domains, but is likely both myristoylated and palmitoylated on its N-terminus. Interestingly, the protein is also dually localized on the surface of the mitochondrion as well as in the flagellum of both insect-stage and the bloodstream form of the parasites. Upon abolishing of global protein acylation or mutation of the myristoylation site POMP39 relocates to the cytosol. RNAimediated ablation of the protein neither causes a growth phenotype in insectstage nor bloodstream form trypanosomes.

Dynamic proteinS-palmitoylation mediates parasite life cycle progression and diverse mechanisms of virulence

“…Our recent review summarized acylation in trypanosomatids these in detail (Goldston et al , 2014). Palmitoylation is necessary for the targeting of these proteins to various organelles including: the flagellar membrane (LmjSMP-1, Ld/TbFlabarin, FCaBP/Calflagins, TbMCA4, TbGPI-PLC, LmjHASPB), the flagellar tip (TbCALP1.3), the flagellar pocket and endosomes (LmjPPEF), the plasma membrane (TcPI-PLC, TbGPI-PLC, LmjHASPB), the sub-pellicular microtubule cytoskeleton (TbCAP5.5), and the mitochondrion (TbPOMP39) (Godsel and Engman, 1999, Hertz-Fowler et al , 2001, Tull et al , 2004, Mills et al , 2007, Emmer et al , 2009, de Paulo Martins et al , 2010, Liu et al , 2010, Proto et al , 2011, Maclean et al , 2012, Lefebvre et al , 2013, Sunter et al , 2013, Albisetti et al , 2015, Tetaud et al , 2016). Several palmitoylated proteins are essential for virulence in trypanosomatids, but the specific PATs have not yet been attributed that palmitoylate these proteins.…”