Involvement of a mitochondrial phosphatase in the regulation of ATP production and insulin secretion in pancreatic β cells
Involvement of a mitochondrial phosphatase in the regulation of ATP production and insulin secretion in pancreatic β cells
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DOI：
10.1016/j.molcel.2005.06.008
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发表时间：
2005-07-22
期刊：
影响因子：
16
通讯作者：
Dixon, JE
中科院分区：
文献类型：
--
作者：
Pagliarini, DJ;Wiley, SE;Dixon, JE
可逆磷酸化是细胞最普遍的翻译后修饰形式，但其在线粒体功能调节中的作用却知之甚少。我们发现，双特异性蛋白酪氨酸磷酸酶 (DS-PTP) 家族的成员 PTPMT1（定位于线粒体 1 的 PTP）几乎完全存在于线粒体中。 PTPMT1 通过 N 端信号序列靶向线粒体，并锚定在内膜的基质面上。胰腺胰岛素瘤细胞系 INS-1 832/ 13 中 PTPMT1 表达的敲低会改变线粒体磷蛋白谱，并显着增强 ATP 产生和胰岛素分泌。这些数据将 PTPMT1 定义为治疗 II 型糖尿病的潜在药物靶点，并强化了线粒体是可逆磷酸化信号传导位点未被充分认识的观念。
Reversible phosphorylation is the cell's most prevalent form of posttranslational modification, yet its role in the regulation of mitochondrial functions is poorly understood. We have discovered that a member of the dual-specific protein tyrosine phosphatase (DS-PTP) family, PTPMT1 (PTP localized to the Mitochondrion 1) resides nearly exclusively in mitochondria. PTPMT1 is targeted to the mitochondrion by an N-terminal signal sequence and is found anchored to the matrix face of the inner membrane. Knockdown of PTPMT1 expression in the pancreatic insulinoma cell line INS-1 832/ 13 alters the mitochondrial phosphoprotein profile and markedly enhances both ATP production and insulin secretion. These data define PTPMT1 as a potential drug target for the treatment of type II diabetes and strengthen the notion that mitochondria are an underappreciated site of signaling by reversible phosphorylation.