The MAP kinase Pmk1 and protein kinase A are required for rotenone resistance in the fission yeast, Schizosaccharomyces pombe.

The MAP kinase Pmk1 and protein kinase A are required for rotenone resistance in the fission yeast, Schizosaccharomyces pombe.
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裂殖酵母 (Schizosaccharomyces pombe) 中的鱼藤酮抗性需要 MAP 激酶 Pmk1 和蛋白激酶 A。

DOI:
10.1016/j.bbrc.2010.07.014
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发表时间:
2010
影响因子:
3.1
通讯作者:
Marcus,Stevan
Marcus,Stevan
中科院分区:
生物学4区
文献类型:
--
作者:
Wang,Yiwei;Gulis,Galina;Buckner,Scott;Johnson,PConnor;Sullivan,Daniel;Busenlehner,Laura;Marcus,Stevan

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鱼藤酮是一种广泛使用的杀虫剂,可引起大鼠帕金森病样症状,并导致培养中的多巴胺能神经元死亡。尽管鱼藤酮是线粒体电子传递链复合物 I 的有效抑制剂,但它可以独立于复合物 I 抑制而诱导多巴胺能神经元死亡。在这里,我们描述了鱼藤酮对裂殖酵母(裂殖酵母)的影响,这种酵母缺乏复合物 I,并且进行鱼藤酮不敏感的细胞呼吸。我们发现,鱼藤酮会诱导经处理的粟酒裂殖酵母细胞中活性氧(ROS)的产生以及线粒体网络的断裂。虽然鱼藤酮仅适度抑制野生型粟酒裂殖酵母细胞的生长,但它对缺乏 ERK 型 MAP 激酶、Pmk1 或蛋白激酶 A (PKA) 的突变体的生长具有强烈抑制作用。相比之下,缺乏 p38 MAP 激酶 Spc1 的细胞对鱼藤酮表现出适度的抵抗力。与这些发现一致,我们提供的证据表明,在鱼藤酮处理的粟酒裂殖酵母细胞中,ROS 的清除需要 Pmk1 和 PKA,而不是 Spc1。我们的结果证明了粟酒裂殖酵母在阐明鱼藤酮复杂的 I 独立分子靶标以及赋予毒素抗性的机制方面的有用性。
Rotenone is a widely used pesticide that induces Parkinson’s disease-like symptoms in rats and death of dopaminergic neurons in culture. Although rotenone is a potent inhibitor of complex I of the mitochondrial electron transport chain, it can induce death of dopaminergic neurons independently of complex I inhibition. Here we describe effects of rotenone in the fission yeast, Schizosaccharomyces pombe, which lacks complex I and carries out rotenone-insensitive cellular respiration. We show that rotenone induces generation of reactive oxygen species (ROS) as well as fragmentation of mitochondrial networks in treated S. pombe cells. While rotenone is only modestly inhibitory to growth of wild type S. pombe cells, it is strongly inhibitory to growth of mutants lacking the ERK-type MAP kinase, Pmk1, or protein kinase A (PKA). In contrast, cells lacking the p38 MAP kinase, Spc1, exhibit modest resistance to rotenone. Consistent with these findings, we provide evidence that Pmk1 and PKA, but not Spc1, are required for clearance of ROS in rotenone treated S. pombe cells. Our results demonstrate the usefulness of S. pombe for elucidating complex I-independent molecular targets of rotenone as well as mechanisms conferring resistance to the toxin.
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DOI: --
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