Molecular symmetry in mitochondrial cardiolipins.
Cardiolipin is a unique mitochondrial phospholipid with an atypical fatty acid profile, but the significance of its acyl specificity has not been understood. We explored the enormous combinatorial diversity among cardiolipin species, which results from the presence of four fatty acids in each molecule, by integrated use of high-performance liquid chromatography, mass spectrometry, diacylglycerol species analysis, fatty acid analysis, and selective cleavage of fatty acids by phospholipase A2. The most abundant cardiolipin species from various organisms and tissues (human heart, human lymphoblasts, rat liver, Drosophila, sea urchin sperm, yeast, mung bean hypocotyls) contained only one or two types of fatty acids, which generated a high degree of structural uniformity and molecular symmetry. However, an exception was found in patients with Barth syndrome, in whom an acyltransferase deficiency led to loss of acyl selectivity and formation of multiple molecular species. These results suggest that restriction of the number of fatty acid species, rather than the selection of a particular kind of fatty acid, is the common theme of eukaryotic cardiolipins. This limits the structural diversity of the cardiolipin species and creates molecular symmetry with implications for the stereochemistry of cardiolipin.
Schlame
Michael
M
Department of Anesthesiology, New York University School of Medicine, 550 First Ave, New York, NY 10016, USA. michael.schlame@med.nyu.edu
Ren
Mindong
M
Xu
Yang
Y
Greenberg
Miriam L
ML
Haller
Ivan
I
D000217:Acyltransferases / Q000172:deficiency; D000293:Adolescent; D000328:Adult; D000818:Animals; D002308:Cardiolipins / Q000737:chemistry*; D002648:Child; D002675:Child, Preschool; D002851:Chromatography, High Pressure Liquid; D004331:Drosophila melanogaster; D005227:Fatty Acids / Q000737:chemistry; D006801:Humans; D007223:Infant; D008928:Mitochondria / Q000737:chemistry*; D009928:Organ Specificity; D027805:Phaseolus; D010741:Phospholipases A / Q000737:chemistry; D054467:Phospholipases A2; D051381:Rats; D012441:Saccharomyces cerevisiae; D012617:Sea Urchins; D013045:Species Specificity
D002308:Cardiolipins; D005227:Fatty Acids; D000217:Acyltransferases; D010741:Phospholipases A; D054467:Phospholipases A2