Mitochondrial Dynamics and Mitochondrial Dysfunction in Diabetes.
Mitochondrial Dynamics and Mitochondrial Dysfunction in Diabetes.
复制标题
DOI：
10.18926/amo/54413
复制
发表时间：
2016-06
影响因子：
0.5
通讯作者：
J. Wada;A. Nakatsuka
中科院分区：
文献类型：
--
作者：
J. Wada;A. Nakatsuka
线粒体参与了活跃和动态的过程，如线粒体的生物发生、分裂、融合和有丝分裂，以维持线粒体和细胞的功能。在肥胖和2型糖尿病中，已有报道称氧化损伤、线粒体含量减少、氧化磷酸化速率降低和活性氧(ROS)产生过多。线粒体的生物发生受多种转录因子的调控，如过氧化物酶体增殖物激活受体γ辅活化子-1α(PGC-1α)、过氧化物酶体增殖物激活受体(PPAR)、雌激素相关受体(ERRs)和核呼吸因子(NRFs)。线粒体融合是由丝裂蛋白1(Mfn1)、丝裂蛋白2(Mfn2)和视神经萎缩1(OPA1)促进的，而分裂是由动态蛋白相关蛋白1(Drp1)的募集所控制的，这些适配蛋白包括线粒体裂变因子(Mff)、49和51 kDa的线粒体动力学蛋白(MiD49和MiD51)以及分裂1(FIS1)。磷酸酶和张力蛋白同源物(PTEN)诱导的假定激酶1(PINK1)和Parkin促进依赖Drp1的线粒体分裂，而外部线粒体适配器MiD51在Drp1招募和Parkin依赖的有丝分裂中是必需的。本文综述了线粒体动力学的分子机制，线粒体动力学在糖尿病和肥胖症中的异常，以及针对线粒体生物发生、分裂、融合和有丝分裂的药物。
The mitochondria are involved in active and dynamic processes, such as mitochondrial biogenesis, fission, fusion and mitophagy to maintain mitochondrial and cellular functions. In obesity and type 2 diabetes, impaired oxidation, reduced mitochondrial contents, lowered rates of oxidative phosphorylation and excessive reactive oxygen species (ROS) production have been reported. Mitochondrial biogenesis is regulated by various transcription factors such as peroxisome proliferator-activated receptor γ coactivator-1α (PGC-1α), peroxisome proliferator-activated receptors (PPARs), estrogen-related receptors (ERRs), and nuclear respiratory factors (NRFs). Mitochondrial fusion is promoted by mitofusin 1 (MFN1), mitofusin 2 (MFN2) and optic atrophy 1 (OPA1), while fission is governed by the recruitment of dynamin-related protein 1 (DRP1) by adaptor proteins such as mitochondrial fission factor (MFF), mitochondrial dynamics proteins of 49 and 51 kDa (MiD49 and MiD51), and fission 1 (FIS1). Phosphatase and tensin homolog (PTEN)-induced putative kinase 1 (PINK1) and PARKIN promote DRP1-dependent mitochondrial fission, and the outer mitochondrial adaptor MiD51 is required in DRP1 recruitment and PARKIN-dependent mitophagy. This review describes the molecular mechanism of mitochondrial dynamics, its abnormality in diabetes and obesity, and pharmaceuticals targeting mitochondrial biogenesis, fission, fusion and mitophagy.