Abstract
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.
Keywords:
CsgA; Drosophila Sniffer; HSD10; Myxococcus xanthus; cardiolipin; phospholipase.
© 2015 Boynton and Shimkets; Published by Cold Spring Harbor Laboratory Press.
Publication types
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Research Support, N.I.H., Extramural
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Research Support, U.S. Gov't, Non-P.H.S.
MeSH terms
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3-Hydroxyacyl CoA Dehydrogenases / genetics
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3-Hydroxyacyl CoA Dehydrogenases / metabolism*
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Alcohol Oxidoreductases / genetics
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Alcohol Oxidoreductases / metabolism*
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Animals
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Bacterial Proteins / genetics
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Bacterial Proteins / metabolism*
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Cardiolipins / metabolism
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Diglycerides / metabolism
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Dihydroxyacetone / metabolism
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Drosophila Proteins / genetics
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Drosophila Proteins / metabolism*
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Drosophila melanogaster / enzymology
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Escherichia coli / genetics
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Humans
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Lipid Droplets / metabolism
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Membrane Proteins / metabolism
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Mutation
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Myxococcus / enzymology
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Oxidation-Reduction
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Phosphates / metabolism
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Phosphatidylglycerols / metabolism
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Recombinant Proteins / genetics
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Recombinant Proteins / metabolism
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Substrate Specificity
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Transferases (Other Substituted Phosphate Groups) / metabolism
Substances
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Bacterial Proteins
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Cardiolipins
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CsgA protein, Myxococcus xanthus
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Diglycerides
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Drosophila Proteins
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Membrane Proteins
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Phosphates
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Phosphatidylglycerols
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Recombinant Proteins
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sni protein, Drosophila
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Alcohol Oxidoreductases
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3-Hydroxyacyl CoA Dehydrogenases
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HSD17B10 protein, human
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Transferases (Other Substituted Phosphate Groups)
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cardiolipin synthetase
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Dihydroxyacetone