Yeast Pgc1p (YPL206c) Controls the Amount of Phosphatidylglycerol via a Phospholipase C-type Degradation Mechanism

Abstract

The product of the open reading frame YPL206c, Pgc1p, of the yeast Saccharomyces cerevisiae displays homology to bacterial and mammalian glycerophosphodiester phosphodiesterases. Deletion of PGC1 causes an accumulation of the anionic phospholipid, phosphatidylglycerol (PG), especially under conditions of inositol limitation. This PG accumulation was not caused by increased production of phosphatidylglycerol phosphate or by decreased consumption of PG in the formation of cardiolipin, the end product of the pathway. PG accumulation in the pgc1⌬ strain was caused rather by inactivation of the PG degradation pathway. Our data demonstrate an existence of a novel regulatory mechanism in the cardiolipin biosynthetic pathway in which Pgc1p is required for the removal of excess PG via a phospholipase C-type degradation mechanism. Cardiolipin (CL)2 is a major mitochondrial anionic phospholipid with important functions in promoting cell growth, anaerobic metabolism, mitochondrial function, and biogenesis (1, 2). Phosphatidylglycerol is not only a metabolic precursor in the biosynthetic pathway leading to the formation of cardiolipin but itself is an important phospholipid; for example it is the sole phospholipid of thylakoid membranes of prokaryotic and eukaryotic oxygenic photosynthetic organisms (3). In mammals, PG is especially important in pulmonary surfactant, an essential fluid produced by alveolar type II cells that covers the entire surface of the lung (4). Considering the importance of this anionic phospholipid, little is known about the mechanisms by which eukaryotic cells control PG membrane composition.In yeast cells, PG is a low abundance phospholipid, present at best as a few tenths of a percent of total cellular phospholipids, even under the conditions of respiratory growth (5). Therefore, PG is considered to be mainly a metabolic precursor to CL. Biosynthesis of CL starts with common intermediates of phospholipid biosynthesis, phosphatidic acid and CDP-diacylglycerol (DAG) (Fig. 1). Phosphatidylglycerol phosphate (PGP) is formed from CDP-DAG and glycerol 3-phosphate. This step is catalyzed by PGP synthase, product of the PGS1/PEL1 gene (6, 7). PGP is subsequently dephosphorylated to form PG. Finally, CL is synthesized in yeast and other eukaryotic organisms from CDP-DAG and PG via a reaction catalyzed by cardiolipin synthase (CRD1) (5,8,9). It is important to note that both CL and PG are subject to intense remodeling subsequent to their de novo synthesis (10).Mitochondrial phospholipid biosynthetic activities in general respond to factors affecting mitochondrial development and function, such as carbon source, growth phase, availability of oxygen, and mutations affecting mitochondrial development and function (11,12). In fact, both enzymatic activities of the CL biosynthetic pathway, PGP synthase and CL synthase, respond to mitochondrial development factors in such a way as to increase the production of CL when cells switch from fermentative to respiratory growth (13-15). A typical feature of yeast phosphol...

Rice and chickpea GDPDs are preferentially influenced by low phosphate and CaGDPD1 encodes an active glycerophosphodiester phosphodiesterase enzyme

“…In P starved S. cerevisiae, significantly higher expression of GDE1 was also observed (Ogawa et al 2000). On the other hand, YPL206c belongs to phospholipase-C-like enzyme superfamily and cleaves phosphatidylglycerol to glycerophosphate (Simockova et al 2008). Apart from their roles in glycerol and phosphate metabolism, GDPDs have been proposed to play diverse roles in other organisms.…”

In Vitro Analysis of the Staphylococcus aureus Lipoteichoic Acid Synthase Enzyme Using Fluorescently Labeled Lipids

“…To gain insight into the LtaS enzyme mechanism, we set out to develop an in vitro assay for the S. aureus eLtaS enzyme. The fluorescently labeled NBD-PG lipid substrate was used in previous studies to follow phospholipase C-type degradation reactions (39), reactions that are similar to that proposed for LtaS. Phospholipase C (PLC)-dependent cleavage of NBD-PG results in the production of fluorescently labeled diacylglycerol (NBD-DAG) (Fig.…”

Cardiolipin Molecular Species with Shorter Acyl Chains Accumulate in Saccharomyces cerevisiae Mutants Lacking the Acyl Coenzyme A-binding Protein Acb1p

“…ϽC16 to CL, unless the PG profile of the crd1acb1 mutant is not representative for the pool of PG available as substrate for Crd1p in the acb1 mutant due to species selective turnover (48) (32). The parent ion scans of newly synthesized PG obtained after 3 h of labeling of crd1 and crd1acb1 cells (Fig.…”