Myxococcus CsgA, Drosophila Sniffer, and human HSD10 are cardiolipin phospholipases.
Myxococcus xanthus development requires CsgA, a member of the short-chain alcohol dehydrogenase (SCAD) family of proteins. We show that CsgA and SocA, a protein that can replace CsgA function in vivo, oxidize the 2'-OH glycerol moiety on cardiolipin and phosphatidylglycerol to produce diacylglycerol (DAG), dihydroxyacetone, and orthophosphate. A lipid extract enriched in DAGs from wild-type cells initiates development and lipid body production in a csgA mutant to bypass the mutational block. This novel phospholipase C-like reaction is widespread. SCADs that prevent neurodegenerative disorders, such as Drosophila Sniffer and human HSD10, oxidize cardiolipin with similar kinetic parameters. HSD10 exhibits a strong preference for cardiolipin with oxidized fatty acids. This activity is inhibited in the presence of the amyloid β peptide. Three HSD10 variants associated with neurodegenerative disorders are inactive with cardiolipin. We suggest that HSD10 protects humans from reactive oxygen species by removing damaged cardiolipin before it induces apoptosis.
Department of Microbiology, University of Georgia, Athens, Georgia 30602, USA.
Tye O'Hara
TO
Boynton
Department of Microbiology, University of Georgia, Athens, Georgia 30602, USA.
Lawrence Joseph
LJ
Shimkets
D015094:3-Hydroxyacyl CoA Dehydrogenases / Q000235:genetics / Q000378:metabolism*; D000429:Alcohol Oxidoreductases / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D001426:Bacterial Proteins / Q000235:genetics / Q000378:metabolism*; D002308:Cardiolipins / Q000378:metabolism; D004075:Diglycerides / Q000378:metabolism; D004098:Dihydroxyacetone / Q000378:metabolism; D029721:Drosophila Proteins / Q000235:genetics / Q000378:metabolism*; D004331:Drosophila melanogaster / Q000201:enzymology; D004926:Escherichia coli / Q000235:genetics; D006801:Humans; D066292:Lipid Droplets / Q000378:metabolism; D008565:Membrane Proteins / Q000378:metabolism; D009154:Mutation; D016940:Myxococcus / Q000201:enzymology; D010084:Oxidation-Reduction; D010710:Phosphates / Q000378:metabolism; D010715:Phosphatidylglycerols / Q000378:metabolism; D011994:Recombinant Proteins / Q000235:genetics / Q000378:metabolism; D013379:Substrate Specificity; D017855:Transferases (Other Substituted Phosphate Groups) / Q000378:metabolism
D001426:Bacterial Proteins; D002308:Cardiolipins; C063576:CsgA protein, Myxococcus xanthus; D004075:Diglycerides; D029721:Drosophila Proteins; D008565:Membrane Proteins; D010710:Phosphates; D010715:Phosphatidylglycerols; D011994:Recombinant Proteins; C487696:sni protein, Drosophila; D000429:Alcohol Oxidoreductases; D015094:3-Hydroxyacyl CoA Dehydrogenases; C108634:HSD17B10 protein, human; D017855:Transferases (Other Substituted Phosphate Groups); C100091:cardiolipin synthetase; D004098:Dihydroxyacetone
CsgA; Drosophila Sniffer; HSD10; Myxococcus xanthus; cardiolipin; phospholipase