PARL partitions the lipid transfer protein STARD7 between the cytosol and mitochondria
PARL partitions the lipid transfer protein STARD7 between the cytosol and mitochondria
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DOI：
10.15252/embj.201797909
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发表时间：
2018-02-15
期刊：
影响因子：
11.4
通讯作者：
Langer, Thomas
中科院分区：
文献类型：
--
作者：
Saita, Shotaro;Tatsuta, Takashi;Langer, Thomas
菱形家族的膜内切割肽酶调节多种细胞过程，对细胞发育和存活至关重要。线粒体内膜菱形蛋白酶PARL的功能与线粒体自噬和细胞凋亡有关，但可能存在其他调节功能。在这里，我们发现含有START结构域的蛋白STARD7是一种线粒体内磷脂酰胆碱的脂质转移蛋白。我们证明，在线粒体输入过程中，parl介导的切割将STARD7分割到细胞质和线粒体膜间空间。STARD7中带负电的氨基酸作为一个分选信号，允许线粒体在PARL切割后释放成熟的STARD7。另一方面，TIM23复合体介导的STARD7的膜插入促进了成熟STARD7的线粒体定位。线粒体STARD7对于磷脂酰胆碱在细胞膜内的积累以及呼吸和嵴形态的维持是必要和充分的。因此，PARL通过STARD7加工保持线粒体膜稳态，并成为线粒体和细胞质之间蛋白质定位的关键调节因子。
Intramembrane-cleaving peptidases of the rhomboid family regulate diverse cellular processes that are critical for development and cell survival. The function of the rhomboid protease PARL in the mitochondrial inner membrane has been linked to mitophagy and apoptosis, but other regulatory functions are likely to exist. Here, we identify the START domain-containing protein STARD7 as an intramitochondrial lipid transfer protein for phosphatidylcholine. We demonstrate that PARL-mediated cleavage during mitochondrial import partitions STARD7 to the cytosol and the mitochondrial intermembrane space. Negatively charged amino acids in STARD7 serve as a sorting signal allowing mitochondrial release of mature STARD7 upon cleavage by PARL. On the other hand, membrane insertion of STARD7 mediated by the TIM23 complex promotes mitochondrial localization of mature STARD7. Mitochondrial STARD7 is necessary and sufficient for the accumulation of phosphatidylcholine in the inner membrane and for the maintenance of respiration and cristae morphogenesis. Thus, PARL preserves mitochondrial membrane homeostasis via STARD7 processing and is emerging as a critical regulator of protein localization between mitochondria and the cytosol.