Department of Cellular and Genetic Medicine, School of Basic Medical Sciences, Fudan University, Shanghai 200032, China.
Acta Biochim Biophys Sin (Shanghai). 2022 Aug 25;54(8):1113-1121. doi: 10.3724/abbs.2022098.
Parkinson's disease (PD) is a neurodegenerative disorder causing severe social and economic burdens. The origin of PD has been usually attributed to mitochondrial dysfunction. To this end, mitochondrial transcription regulators become attractive subjects for understanding PD pathogenesis. Previously, we found that the expression of mitochondrial transcription termination factor 3 (MTERF3) was reduced in MPP+-induced mice model of PD. In the present study, we probe the function of MTERF3 and its role in MPP+-induced cellular model of PD. Initially, we observe that MTERF3 expression is also reduced in MPP+-induced cellular model of PD, which can be mainly attributed to the increase of MTERF3 degradation. Next, we examine the effect of MTERF3 knockdown and overexpression on the replication, transcription, and translation of mitochondrial DNA (mtDNA). We show that knockdown and overexpression of MTERF3 have opposite effects on mtDNA transcript level but similar effects on mtDNA expression level, in line with MTERF3's dual roles in mtDNA transcription and translation. In addition, we examine the effect of MTERF3 knockdown and overexpression on mitochondrial function with and without MPP+ treatment, and find that MTERF3 seems to play a generally protective role in MPP+-induced mitochondrial dysfunction. Together, this work suggests a regulatory role of MTERF3 in MPP+-induced cellular model of PD and may provide clues in designing novel therapeutics against PD.
帕金森病（PD）是一种神经退行性疾病，给社会和经济带来了严重的负担。PD 的起源通常归因于线粒体功能障碍。为此，线粒体转录调节因子成为理解 PD 发病机制的有吸引力的研究对象。之前，我们发现线粒体转录终止因子 3（MTERF3）在 MPP+诱导的 PD 小鼠模型中的表达降低。在本研究中，我们探究了 MTERF3 的功能及其在 MPP+诱导的 PD 细胞模型中的作用。首先，我们观察到 MPP+诱导的 PD 细胞模型中 MTERF3 的表达也降低，这主要归因于 MTERF3 降解的增加。接下来，我们研究了 MTERF3 敲低和过表达对线粒体 DNA（mtDNA）复制、转录和翻译的影响。结果表明，MTERF3 的敲低和过表达对 mtDNA 转录水平有相反的影响，但对 mtDNA 表达水平有相似的影响，这与 MTERF3 在 mtDNA 转录和翻译中的双重作用一致。此外，我们研究了 MPP+处理前后 MTERF3 敲低和过表达对线粒体功能的影响，发现 MTERF3 在 MPP+诱导的线粒体功能障碍中似乎发挥了普遍的保护作用。总之，这项工作表明 MTERF3 在 MPP+诱导的 PD 细胞模型中具有调节作用，并可能为设计针对 PD 的新型治疗方法提供线索。
