The Donnelly Centre, University of Toronto, Toronto, Canada.
Laboratorio de Biología de Gusanos. Unidad Mixta, Departamento de Biociencias, Facultad de Química, Universidad de la República - Institut Pasteur de Montevideo, Montevideo, Uruguay.
Elife. 2020 Aug 3;9:e56376. doi: 10.7554/eLife.56376.
Parasitic helminths use two benzoquinones as electron carriers in the electron transport chain. In normoxia, they use ubiquinone (UQ), but in anaerobic conditions inside the host, they require rhodoquinone (RQ) and greatly increase RQ levels. We previously showed the switch from UQ to RQ synthesis is driven by a change of substrates by the polyprenyltransferase COQ-2 (Del Borrello et al., 2019; Roberts Buceta et al., 2019); however, the mechanism of substrate selection is not known. Here, we show helminths synthesize two splice forms, and , and the specific exon is only found in species that synthesize RQ. We show that in COQ-2e is required for efficient RQ synthesis and survival in cyanide. Importantly, parasites switch from COQ-2a to COQ-2e as they transit into anaerobic environments. We conclude helminths switch from UQ to RQ synthesis principally via changes in the alternative splicing of
寄生虫利用两种苯醌作为电子传递链中的电子载体。在正常氧条件下，它们使用泛醌（UQ），但在宿主内的厌氧条件下，它们需要红屈菜醌（RQ）并大大增加 RQ 水平。我们之前表明，通过聚异戊二烯转移酶 COQ-2（Del Borrello 等人，2019 年；Roberts Buceta 等人，2019 年）改变底物，从 UQ 到 RQ 合成的转变是由底物引起的；然而，底物选择的机制尚不清楚。在这里，我们表明寄生虫合成两种剪接形式和，并且只有在合成 RQ 的物种中才发现特定的外显子。我们表明，在氰化物中，COQ-2e 对于有效的 RQ 合成和生存是必需的。重要的是，寄生虫在过渡到厌氧环境时从 COQ-2a 切换到 COQ-2e。我们的结论是，寄生虫主要通过 COQ-2 的选择性剪接从 UQ 合成切换到 RQ 合成
