A mitochondrial phosphatase required for cardiolipin biosynthesis: the PGP phosphatase Gep4
Open Access
- 18 May 2010
- journal article
- research article
- Published by Springer Science and Business Media LLC in The EMBO Journal
- Vol. 29 (12), 1976-1987
- https://doi.org/10.1038/emboj.2010.98
Abstract
Cardiolipin (CL), a unique dimeric phosphoglycerolipid predominantly present in mitochondrial membranes, has pivotal functions for the cellular energy metabolism, mitochondrial dynamics and the initiation of apoptotic pathways. Perturbations in the mitochondrial CL metabolism cause cardiomyopathy in Barth syndrome. Here, we identify a novel phosphatase in the mitochondrial matrix space, Gep4, and demonstrate that it dephosphorylates phosphatidylglycerolphosphate to generate phosphatidylglycerol, an essential step during CL biosynthesis. Expression of a mitochondrially targeted variant of Escherichia coli phosphatase PgpA restores CL levels in Gep4‐deficient cells, indicating functional conservation. A genetic epistasis analysis combined with the identification of intermediates of CL biosynthesis allowed us to integrate Gep4 in the CL‐biosynthetic pathway and assign an essential function during early steps of CL synthesis to Tam41, which has previously been shown to be essential for the maintenance of normal CL levels. Our experiments provide the framework for the further dissection of mechanisms that are required for accumulation and maintenance of CL levels in mitochondria.Keywords
This publication has 66 references indexed in Scilit:
- Loss of Mitochondrial DNA in the Yeast Cardiolipin Synthase crd1 Mutant Leads to Up-regulation of the Protein Kinase Swe1p That Regulates the G2/M Transition*Online Journal of Public Health Informatics, 2010
- Identification of a Cardiolipin-specific Phospholipase Encoded by the Gene CLD1 (YGR110W) in YeastOnline Journal of Public Health Informatics, 2009
- Cellular functions of cardiolipin in yeastBiochimica et Biophysica Acta (BBA) - Molecular Cell Research, 2009
- Bacterial expression and purification of Interleukin-2 Tyrosine kinase: Single step separation of the chaperonin impurityProtein Expression and Purification, 2008
- Yeast Pgc1p (YPL206c) Controls the Amount of Phosphatidylglycerol via a Phospholipase C-type Degradation MechanismOnline Journal of Public Health Informatics, 2008
- Structures and physiological roles of 13 integral lipids of bovine heart cytochrome c oxidaseThe EMBO Journal, 2007
- Identification of Tam41 maintaining integrity of the TIM23 protein translocator complex in mitochondriaThe Journal of cell biology, 2006
- Ups1p, a conserved intermembrane space protein, regulates mitochondrial shape and alternative topogenesis of Mgm1pThe Journal of cell biology, 2006
- Getting started with yeastMethods in Enzymology, 2002
- Evidence for Segregation of Sphingomyelin and Cholesterol during Formation of Copi-Coated VesiclesThe Journal of cell biology, 2000