Troulinaki Kostoula, Büttner Sven, Marsal Cots Anaïs, Maida Simona, Meyer Katharina, Bertan Fabio, Gioran Anna, Piazzesi Antonia, Fornarelli Alessandra, Nicotera Pierluigi, Bano Daniele
German Center for Neurodegenerative Diseases (DZNE), Bonn, Germany.
Cell Death Discov. 2018 Jan 29;4:2. doi: 10.1038/s41420-017-0005-6. eCollection 2018 Dec.
Impaired mitochondrial energy metabolism contributes to a wide range of pathologic conditions, including neurodegenerative diseases. Mitochondrial apoptosis-inducing factor (AIF) is required for the correct maintenance of mitochondrial electron transport chain. An emerging body of clinical evidence indicates that several mutations in the gene are causally linked to severe forms of mitochondrial disorders. Here we investigate the consequence of WAH-1/AIF deficiency in the survival of the nematode . Moreover, we assess the survival of . strains expressing a disease-associated WAH-1/AIF variant. We demonstrate that downregulation compromises the function of the oxidative phosphorylation system and reduces . lifespan. Notably, the loss of respiratory subunits induces a nuclear-encoded mitochondrial stress response independently of an evident increase of oxidative stress. Overall, our data pinpoint an evolutionarily conserved role of WAH-1/AIF in the maintenance of proper mitochondrial activity.
线粒体能量代谢受损会导致多种病理状况，包括神经退行性疾病。线粒体凋亡诱导因子（AIF）是正确维持线粒体电子传递链所必需的。越来越多的临床证据表明，该基因中的几个突变与严重形式的线粒体疾病存在因果关系。在这里，我们研究了WAH-1/AIF缺陷对线虫生存的影响。此外，我们评估了表达与疾病相关的WAH-1/AIF变体的菌株的生存情况。我们证明，WAH-1/AIF的下调会损害氧化磷酸化系统的功能并缩短线虫寿命。值得注意的是，呼吸亚基的缺失会独立于氧化应激的明显增加而诱导核编码的线粒体应激反应。总体而言，我们的数据确定了WAH-1/AIF在维持适当线粒体活性方面的进化保守作用。
