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

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.

journal_name

Genes Dev

journal_title

Genes & development

authors

Boynton TO,Shimkets LJ

doi

10.1101/gad.268482.115

subject

Has Abstract

pub_date

2015-09-15 00:00:00

pages

1903-14

issue

18

eissn

0890-9369

issn

1549-5477

pii

gad.268482.115

journal_volume

29

pub_type

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