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.