Specific degradation of phosphatidylglycerol is necessary for proper mitochondrial morphology and function

In yeast, phosphatidylglycerol (PG) is a minor phospholipid under standard conditions; it can be utilized for cardiolipin (CL) biosynthesis by CL synthase, Crd1p, or alternatively degraded by the phospholipase Pgc1p. The Saccharomyces cerevisiae deletion mutants crd1 Delta and pgc1 Delta both accumulate PG. Based on analyses of the phospholipid content of pgc1 Delta, and crd1 Delta yeast, we revealed that in yeast mitochondria, two separate pools of PG are present, which differ in their fatty acid composition and accessibility for Pgcl p-catalyzed degradation. In contrast to CL-deficient crd1 Delta yeast, the pgc1 Delta mutant contains normal levels of CL. This makes the pgc1 Delta strain a suitable model to study the effect of accumulation of PG per se. Using fluorescence microscopy, we show that accumulation of PG with normal levels of CL resulted in increased fragmentation of mitochondria, while in the absence of CL, accumulation of PG led to the formation of large mitochondrial sheets. We also show that pgc1 Delta mitochondria exhibited increased respiration rates due to increased activity of cytochrome c oxidase. Taken together, our results indicate that not only a lack of anionic phospholipids, but also excess PG, or unbalanced ratios of anionic phospholipids in mitochondrial membranes, have harmful consequences on mitochondrial morphology and function. (C) 2015 Elsevier B.V. All rights reserved.