Dulbecco-Telethon Institute, Venetian Institute of Molecular Medicine, Padova, Italy.
EMBO Rep. 2010 Nov;11(11):854-60. doi: 10.1038/embor.2010.151. Epub 2010 Oct 8.
Trichoplein/mitostatin (TpMs) is a keratin-binding protein that partly colocalizes with mitochondria and is often downregulated in epithelial cancers, but its function remains unclear. In this study, we report that TpMs regulates the tethering between mitochondria and endoplasmic reticulum (ER) in a Mitofusin 2 (Mfn2)-dependent manner. Subcellular fractionation and immunostaining show that TpMs is present at the interface between mitochondria and ER. The expression of TpMs leads to mitochondrial fragmentation and loosens tethering with ER, whereas its silencing has opposite effects. Functionally, the reduced tethering by TpMs inhibits apoptosis by Ca(2+)-dependent stimuli that require ER-mitochondria juxtaposition. Biochemical and genetic evidence support a model in which TpMs requires Mfn2 to modulate mitochondrial shape and tethering. Thus, TpMs is a new regulator of mitochondria-ER juxtaposition.
毛角蛋白/trichoplein（TpMs）是一种角蛋白结合蛋白，部分与线粒体共定位，在上皮性肿瘤中常下调，但功能尚不清楚。本研究报道 TpMs 以依赖于线粒体融合蛋白 2（Mfn2）的方式调节线粒体与内质网（ER）之间的连接。亚细胞分级分离和免疫染色显示 TpMs 存在于线粒体和 ER 之间的界面处。TpMs 的表达导致线粒体碎片化并松解与 ER 的连接，而其沉默则有相反的作用。功能上，TpMs 通过减少 Ca(2+)-依赖性刺激所需的 ER-线粒体并列来抑制细胞凋亡。生化和遗传证据支持 TpMs 需要 Mfn2 来调节线粒体形状和连接的模型。因此，TpMs 是线粒体-ER 并列的新调节因子。
