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 crd1Δ and pgc1Δ both accumulate PG. Based on analyses of the phospholipid content of pgc1Δ and crd1Δ yeast, we revealed that in yeast mitochondria, two separate pools of PG are present, which differ in their fatty acid composition and accessibility for Pgc1p-catalyzed degradation. In contrast to CL-deficient crd1Δ yeast, the pgc1Δ mutant contains normal levels of CL. This makes the pgc1Δ 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 pgc1Δ 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.
Department of Membrane Biochemistry, Institute of Animal Biochemistry and Genetics, Slovak Academy of Sciences, Ivanka pri Dunaji, Slovakia.
Lucia
L
Pokorná
Department of Biochemistry, Faculty of Natural Sciences, Comenius University, Bratislava, Slovakia.
Petra
P
Čermáková
Department of Biochemistry, Faculty of Natural Sciences, Comenius University, Bratislava, Slovakia.
Anton
A
Horváth
Department of Physiology, School of Medicine, Johns Hopkins University, Baltimore, MD, USA.
Matthew G
MG
Baile
Department of Physiology, School of Medicine, Johns Hopkins University, Baltimore, MD, USA.
Steven M
SM
Claypool
Department of Membrane Biochemistry, Institute of Animal Biochemistry and Genetics, Slovak Academy of Sciences, Ivanka pri Dunaji, Slovakia.
Peter
P
Griač
Microscopy Unit, Institute of Experimental Medicine, Academy of Sciences of the Czech Republic, Prague, Czech Republic.
Jan
J
Malínský
Department of Membrane Biochemistry, Institute of Animal Biochemistry and Genetics, Slovak Academy of Sciences, Ivanka pri Dunaji, Slovakia. Electronic address: Maria.Balazova@savba.sk.
Mária
M
Balážová
D002308:Cardiolipins / Q000096:biosynthesis; D003576:Electron Transport Complex IV / Q000378:metabolism; D008928:Mitochondria / Q000378:metabolism* / Q000648:ultrastructure; D010715:Phosphatidylglycerols / Q000378:metabolism*; D010740:Phospholipases / Q000502:physiology; D012441:Saccharomyces cerevisiae / Q000378:metabolism*
D002308:Cardiolipins; D010715:Phosphatidylglycerols; D003576:Electron Transport Complex IV; D010740:Phospholipases
Mitochondria; Morphology; Phosphatidylglycerol; Respiration; Yeast