Loss of protein association causes cardiolipin degradation in Barth syndrome.
Loss of protein association causes cardiolipin degradation in Barth syndrome.
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DOI：
10.1038/nchembio.2113
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发表时间：
2016-08
影响因子：
14.8
通讯作者：
Schlame M
中科院分区：
文献类型：
--
作者：
Xu Y;Phoon CK;Berno B;D'Souza K;Hoedt E;Zhang G;Neubert TA;Epand RM;Ren M;Schlame M
心磷脂是一种特殊的线粒体磷脂，它与蛋白质具有高亲和力，并稳定参与氧化磷酸化的超复合体的组装。我们发现，心磷脂在蛋白质复合体中的隔离是保护其免受降解的关键。心磷脂的周转几乎比其他磷脂的周转慢一个数量级。然而，在Barth综合征中，心磷脂通过中间体单溶心磷脂迅速降解。诱导超复合体组装的处理降低了心磷脂的周转率和单溶心磷脂的浓度，而超复合体的解离则相反。我们的数据表明，心磷脂通过其与蛋白质的联系唯一地保护其免受正常脂代谢的影响，但在这种联系受到损害的Barth综合征中，心磷脂变得不稳定，从而导致单溶-心磷脂的积累。
Cardiolipin is a specific mitochondrial phospholipid that has a high affinity for proteins and that stabilizes the assembly of supercomplexes involved in oxidative phosphorylation. We found that sequestration of cardiolipin in protein complexes is critical to protect it from degradation. The turnover of cardiolipin is slower by almost an order of magnitude than the turnover of other phospholipids. However, in Barth syndrome, cardiolipin is rapidly degraded via the intermediate monolyso-cardiolipin. Treatments that induce supercomplex assembly decrease the turnover of cardiolipin and the concentration of monolyso-cardiolipin whereas dissociation of supercomplexes has the opposite effect. Our data suggest that cardiolipin is uniquely protected from normal lipid turnover by its association with proteins, but in Barth syndrome, where this association is compromised, cardiolipin becomes unstable, which causes the accumulation of monolyso-cardiolipin.