Myxococcus CsgA, Drosophila Sniffer, and human HSD10 are cardiolipin phospholipases.
Myxococcus CsgA, Drosophila Sniffer, and human HSD10 are cardiolipin phospholipases.
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DOI：
10.1101/gad.268482.115
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发表时间：
2015-09-15
影响因子：
10.5
通讯作者：
Shimkets LJ
中科院分区：
文献类型：
--
作者：
Boynton TO;Shimkets LJ
黄色粘球菌的发育需要CsgA，它是短链酒精脱氢酶(SCAD)家族的成员。Boynton和Shimkets表明，CsgA和SOCA氧化心磷脂和磷脂酰甘油上的2‘-羟基甘油部分生成二酰基甘油、二羟基丙酮和正磷酸盐。防止神经退行性疾病的SCADs，如果蝇嗅探器和人类HSD17B10，以相似的动力学参数氧化心磷脂。黄色粘球菌的发育需要CsgA，它是短链酒精脱氢酶(SCAD)家族的成员。我们发现CsgA和SOCA是一种可以在体内取代CsgA功能的蛋白质，它们氧化心磷脂和磷脂酰甘油上的2‘-羟基甘油部分生成二酰基甘油(DAG)、二羟丙酮和正磷酸盐。从野生型细胞中提取的富含DAG的脂类提取物可启动CsgA突变体的发育和脂体生产，以绕过突变块。这种新的磷脂酶C反应广泛存在。防止神经退行性疾病的SCADs，如果蝇嗅探器和人类HSD10，以相似的动力学参数氧化心磷脂。HSD10表现出对含有氧化脂肪酸的心磷脂的强烈偏好。这种活性在淀粉样蛋白β肽的存在下被抑制。与神经退行性疾病相关的三种HSD10变体在心磷脂中不起作用。我们认为，HSD10通过在诱导细胞凋亡之前清除受损的心磷脂来保护人类免受活性氧的伤害。
Myxococcus xanthus development requires CsgA, a member of the short-chain alcohol dehydrogenase (SCAD) family of proteins. Boynton and Shimkets show that CsgA and SocA oxidize the 2′-OH glycerol moiety on cardiolipin and phosphatidylglycerol to produce diacylglycerol, dihydroxyacetone, and orthophosphate. SCADs that prevent neurodegenerative disorders, such as Drosophila Sniffer and human HSD17B10, oxidize cardiolipin with similar kinetic parameters. 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.
影响因子：
2.4
作者：
Kambayashi Y;Takekoshi S;Tanino Y;Watanabe K;Nakano M;Hitomi Y;Takigawa T;Ogino K;Yamamoto Y
通讯作者：
Yamamoto Y