TY - JOUR
T1 - Specific degradation of phosphatidylglycerol is necessary for proper mitochondrial morphology and function
AU - Pokorná, Lucia
AU - Čermáková, Petra
AU - Horváth, Anton
AU - Baile, Matthew G.
AU - Claypool, Steven M.
AU - Griač, Peter
AU - Malínský, Jan
AU - Balážová, Mária
N1 - Publisher Copyright:
© 2015 Elsevier B.V. All rights reserved.
PY - 2016/1/1
Y1 - 2016/1/1
N2 - 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.
AB - 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.
KW - Mitochondria
KW - Morphology
KW - Phosphatidylglycerol
KW - Respiration
KW - Yeast
UR - http://www.scopus.com/inward/record.url?scp=84945917809&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84945917809&partnerID=8YFLogxK
U2 - 10.1016/j.bbabio.2015.10.004
DO - 10.1016/j.bbabio.2015.10.004
M3 - Article
C2 - 26482708
AN - SCOPUS:84945917809
SN - 0005-2728
VL - 1857
SP - 34
EP - 45
JO - Biochimica et Biophysica Acta - Bioenergetics
JF - Biochimica et Biophysica Acta - Bioenergetics
IS - 1
ER -