Mcp1 and Mcp2, two novel proteins involved in mitochondrial lipid homeostasis
Mcp1 and Mcp2, two novel proteins involved in mitochondrial lipid homeostasis
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DOI：
10.1242/jcs.121244
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发表时间：
2013-08-15
影响因子：
4
通讯作者：
Dimmer, Kai Stefan
中科院分区：
文献类型：
--
作者：
Tan, Tao;Oezbalci, Cagakan;Dimmer, Kai Stefan
酵母线粒体外膜(MOM)蛋白MDM10至少参与三个不同的过程：(1)线粒体与内质网的结合和线粒体脂平衡；(2)MOM蛋白的膜组装；(3)线粒体的遗传和形态发生。为了破译mdm10在线粒体功能中的确切作用，我们筛选了mdm10 Delta突变体严重生长缺陷的高拷贝抑制因子。我们鉴定了两个新的线粒体蛋白(开放阅读框YOR228c和YLR253w)，我们将其命名为Mdm10互补蛋白(MCP)1和Mcp2。Mcp1或Mcp2的过表达可以恢复缺失MDm10的线粒体呼吸链复合体的形态和稳定性的改变，但不能挽救已观察到的MOM蛋白组装缺陷。脂质分析表明，Mcp1和Mcp2水平的升高恢复了缺乏MDm10的细胞线粒体磷脂和麦角甾醇稳态的变化。总的来说，这项工作确定了两种新的蛋白质，它们在线粒体脂质稳态中发挥作用，并描述了MDM10在麦角固醇运输中的作用。
The yeast mitochondrial outer membrane (MOM) protein Mdm10 is involved in at least three different processes: (1) association of mitochondria with the endoplasmic reticulum and mitochondrial lipid homeostasis (2) membrane assembly of MOM proteins, and (3) inheritance and morphogenesis of mitochondria. To decipher the precise role of Mdm10 in mitochondrial function, we screened for high-copy suppressors of the severe growth defect of the mdm10 Delta mutant. We identified two novel mitochondrial proteins (open reading frames YOR228c and YLR253w) that we named Mdm10 complementing protein (Mcp) 1 and Mcp2. Overexpression of Mcp1 or Mcp2 restores the alterations in morphology and stability of respiratory chain complexes of mitochondria devoid of Mdm10, but the observed defect in assembly of MOM proteins is not rescued. Lipid analysis demonstrates that elevated levels of Mcp1 and Mcp2 restore the alterations in mitochondrial phospholipid and ergosterol homeostasis in cells lacking Mdm10. Collectively, this work identifies two novel proteins that play a role in mitochondrial lipid homeostasis and describes a role of Mdm10 in ergosterol trafficking.