Premium
Phosphatidylglycerophosphate synthase associates with a mitochondrial inner membrane complex and is essential for growth of T rypanosoma brucei
Author(s) -
Serricchio Mauro,
Bütikofer Peter
Publication year - 2013
Publication title -
molecular microbiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.857
H-Index - 247
eISSN - 1365-2958
pISSN - 0950-382X
DOI - 10.1111/mmi.12116
Subject(s) - cardiolipin , biology , trypanosoma brucei , mitochondrion , biochemistry , atp synthase , inner mitochondrial membrane , phosphatidylglycerol , enzyme , microbiology and biotechnology , phospholipid , gene , membrane , phosphatidylcholine
Summary Maintenance of the lipid composition is important for proper function and homeostasis of the mitochondrion. In T rypanosoma brucei , the enzymes involved in the biosynthesis of the mitochondrial phospholipid, phosphatidylglycerol ( PG ), have not been studied experimentally. We now report the characterization of T . brucei phosphatidylglycerophosphate synthase ( TbPgps ), the rate‐limiting enzyme in PG formation, which was identified based on its homology to other eukaryotic Pgps . Lipid quantification and metabolic labelling experiments show that TbPgps gene knock‐down results in loss of PG and a reduction of another mitochondria‐specific phospholipid, cardiolipin. Using immunohistochemistry and immunoblotting of digitonin‐isolated mitochondria, we show that TbPgps localizes to the mitochondrion. Moreover, reduced TbPgps expression in T . brucei procyclic forms leads to alterations in mitochondrial morphology, reduction in the amounts of respiratory complexes III and IV and, ultimately, parasite death. Using native polyacrylamide gel electrophoresis we demonstrate for the first time in a eukaryotic organism that TbPgps is a component of a 720 kDa protein complex, co‐migrating with T . brucei cardiolipin synthase and cytochrome c 1, a protein of respiratory complex III .