The membrane scaffold SLP2 anchors a proteolytic hub in mitochondria containing PARL and the i-AAA protease YME1L
The membrane scaffold SLP2 anchors a proteolytic hub in mitochondria containing PARL and the i-AAA protease YME1L
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DOI：
10.15252/embr.201642698
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发表时间：
2016-12-01
期刊：
影响因子：
7.7
通讯作者：
Langer, Thomas
中科院分区：
文献类型：
--
作者：
Wai, Timothy;Saita, Shotaro;Langer, Thomas
SPFH （stomatin, prohibitin, flotillin, HflC/K）超家族由形成环状结构的支架蛋白组成，并在多种细胞膜中局部指定蛋白质脂质组成。口蛋白样蛋白2 （SLP2）是这个超家族的成员，定位于线粒体内膜（IM），在那里它起着膜组织者的作用。在这里，我们报道了SLP2锚定了一个由菱形蛋白酶PARL和i-AAA蛋白酶YME1L组成的大型蛋白酶复合物，我们将其称为SPY复合物（SLP2-PARL-YME1L）。SPY复合体中与SLP2的关联调节parl介导的pten诱导的激酶PINK1和线粒体中磷酸酶PGAM5的加工。此外，SLP2抑制应激激活肽酶OMA1， OMA1可以结合SLP2并在去极化线粒体中切割PGAM5。SLP2限制oma1介导的动力蛋白样GTPase OPA1的加工，允许饥饿条件下应激诱导的线粒体低灌注。总之，我们的研究结果揭示了SLP2膜支架在IM蛋白酶的空间组织调节线粒体动力学、质量控制和细胞存活方面的重要作用。
The SPFH (stomatin, prohibitin, flotillin, HflC/K) superfamily is composed of scaffold proteins that form ring-like structures and locally specify the protein-lipid composition in a variety of cellular membranes. Stomatin-like protein 2 (SLP2) is a member of this superfamily that localizes to the mitochondrial inner membrane (IM) where it acts as a membrane organizer. Here, we report that SLP2 anchors a large protease complex composed of the rhomboid protease PARL and the i-AAA protease YME1L, which we term the SPY complex (for SLP2-PARL-YME1L). Association with SLP2 in the SPY complex regulates PARL-mediated processing of PTEN-induced kinase PINK1 and the phosphatase PGAM5 in mitochondria. Moreover, SLP2 inhibits the stress-activated peptidase OMA1, which can bind to SLP2 and cleaves PGAM5 in depolarized mitochondria. SLP2 restricts OMA1-mediated processing of the dynamin-like GTPase OPA1 allowing stress-induced mitochondrial hyperfusion under starvation conditions. Together, our results reveal an important role of SLP2 membrane scaffolds for the spatial organization of IM proteases regulating mitochondrial dynamics, quality control, and cell survival.