Myxococcus CsgA, Drosophila Sniffer, and human HSD10 are cardiolipin phospholipases

Genes & Development
Tye O'Hara Boynton, Lawrence J Shimkets

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.

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Citations

Jun 16, 2016·Frontiers in Microbiology·José Muñoz-DoradoJuana Pérez
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Aug 24, 2021·Journal of Inherited Metabolic Disease·Jan Dudek, Christoph Maack
Nov 5, 2021·Proceedings of the National Academy of Sciences of the United States of America·Y HoangLee Kroos

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