PDF(Pubmed)
Abstract：
The PTEN-induced kinase 1 (PINK1)-Parkin pathway plays a vital role in maintaining a healthy pool of mitochondria in higher eukaryotic cells. While the downstream components of this pathway are well understood, the upstream triggers remain less explored. In this study, we conducted an extensive analysis of inhibitors targeting various mitochondrial electron transport chain (ETC) complexes to investigate their potential as activators of the PINK1-Parkin pathway. We identified cloflucarban, an antibacterial compound, as a novel pathway activator that simultaneously inhibits mitochondrial complexes III and V, and V. RNA interference (RNAi) confirmed that the dual inhibition of these complexes activates the PINK1-Parkin pathway. Intriguingly, we discovered that albumin, specifically bovine serum albumin (BSA) and human serum albumin (HSA) commonly present in culture media, can hinder carbonyl cyanide m-chlorophenyl hydrazone (CCCP)-induced pathway activation. However, cloflucarban\'s efficacy remains unaffected by albumin, highlighting its reliability for studying the PINK1-Parkin pathway. This study provides insights into the activation of the upstream PINK1-Parkin pathway and underscores the influence of culture conditions on research outcomes. Cloflucarban emerges as a promising tool for investigating mitochondrial quality control and neurodegenerative diseases.
摘要：
PTEN诱导的激酶1（PINK1）-Parkin途径在维持高等真核细胞中线粒体的健康库中起着至关重要的作用。虽然这种途径的下游成分是众所周知的，上游触发因素仍较少探索。在这项研究中,我们对靶向各种线粒体电子传递链(ETC)复合物的抑制剂进行了广泛分析,以研究它们作为PINK1-Parkin通路激活剂的潜力.我们发现了氯氟卡班，一种抗菌化合物，作为同时抑制线粒体复合物III和V的新型通路激活剂，和V.RNA干扰(RNAi)证实这些复合物的双重抑制激活了PINK1-Parkin途径。有趣的是，我们发现白蛋白,特别是牛血清白蛋白（BSA）和人血清白蛋白（HSA）通常存在于培养基中，可以阻碍羰基氰化物间氯苯酰腙（CCCP）诱导的途径活化。然而,氯氟卡班的疗效不受白蛋白的影响，强调其研究PINK1-Parkin通路的可靠性。这项研究提供了对上游PINK1-Parkin途径激活的见解，并强调了培养条件对研究结果的影响。Cloflucarban成为研究线粒体质量控制和神经退行性疾病的有前途的工具。
