The fungal mitochondrial membrane protein, BbOhmm, antagonistically controls hypoxia tolerance
The fungal mitochondrial membrane protein, BbOhmm, antagonistically controls hypoxia tolerance
复制标题
真菌线粒体膜蛋白 BbOhmm 拮抗地控制缺氧耐受性
DOI：
10.1111/1462-2920.14910
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发表时间：
2020-01-23
影响因子：
5.1
通讯作者：
Zhang, Yongjun
中科院分区：
文献类型：
--
作者：
He, Zhangjiang;Zhao, Xin;Zhang, Yongjun
对宿主组织中低氧环境的适应是微生物病原体，特别是真菌成功感染目标宿主的关键。然而，大多数病原体耐缺氧的潜在机制尚不清楚。一种线粒体蛋白BbOHm被证明可以限制昆虫真菌病原体球孢白僵菌的抗氧化性和毒力。在这里，我们发现BbOHMM对昆虫血腔的低氧适应产生了负面影响，同时调节了与呼吸相关的事件、血红素合成和线粒体铁稳态。哺乳动物类固醇调节元件结合蛋白(SREBPs)的同源物BbSre1被证明参与BbOHMM介导的LO适应。BbSre1的失活导致对低氧和氧化应激的敏感性显著增加。与Delta BbOHm类似，Delta BbSre1或Delta BbOhm Delta BbSre1双突变体积累了高水平的血红素和线粒体铁，在低氧胁迫下调节类似的途径。在Delta BbOHm细胞中，BbSre1转录活性和核输入受到抑制，并受到细胞内活性氧(ROS)和氧水平的影响。这些发现导致了一个新的模型，在该模型中，BbOHMM影响ROS稳态，与可用氧结合来控制BbSre1的转录活性，BbSre1反过来通过调节线粒体铁稳态、血红素合成和呼吸相关基因来介导LO适应。
Adaptation to low-oxygen (LO) environment in host tissues is crucial for microbial pathogens, particularly fungi, to successfully infect target hosts. However, the underlying mechanisms responsible for hypoxia tolerance in most pathogens are poorly understood. A mitochondrial protein, BbOhmm, is demonstrated to limit oxidative stress resistance and virulence in the insect fungal pathogen, Beauveria bassiana. Here, we found that BbOhmm negatively affected hypoxic adaptation in the insect haemocoel while regulating respiration-related events, heme synthesis and mitochondrial iron homeostasis. A homologue of the mammalian sterol regulatory element-binding proteins (SREBPs), BbSre1, was shown to be involved in BbOhmm-mediated LO adaptation. Inactivation of BbSre1 resulted in a significant increase in sensitivity to hypoxic and oxidative stress. Similar to Delta BbOhmm, Delta BbSre1 or the Delta BbOhmm Delta BbSre1 double mutant accumulated high levels of heme and mitochondrial iron, regulating the similar pathways during hypoxic stress. BbSre1 transcriptional activity and nuclear import were repressed in Delta BbOhmm cells and affected by intracellular reactive oxygen species (ROS) and oxygen levels. These findings have led to a new model in which BbOhmm affects ROS homeostasis in combination with available oxygen to control the transcriptional activity of BbSre1, which in turn mediates LO adaptation by regulating mitochondrial iron homeostasis, heme synthesis and respiration-implicated genes.