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 ΔBbOhmm , ΔBbSre1 or the ΔBbOhmmΔBbSre1 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 ΔBbOhmm 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.

中文翻译：

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真菌线粒体膜蛋白BbOhmm拮抗缺氧耐受性。

适应宿主组织中的低氧（LO）环境对于微生物病原体（尤其是真菌）成功感染目标宿主至关重要。但是，对于大多数病原体耐缺氧的潜在机制了解甚少。线粒体蛋白BbOhmm被证明可限制昆虫真菌病原体球孢白僵菌的氧化应激抗性和毒力。在这里，我们发现BbOhmm对昆虫血细胞中的低氧适应有负面影响，同时调节呼吸相关事件，血红素合成和线粒体铁稳态。哺乳动物固醇调节元件结合蛋白（SREBPs）的同系物BbSre1被证明与BbOhmm介导的LO适应有关。BbSre1的失活导致对缺氧和氧化应激的敏感性显着提高。与ΔBbOhmm相似，ΔBbSre1或ΔBbOhmmΔBbSre1双重突变体积累了高水平的血红素和线粒体铁，从而调节了低氧应激期间的相似途径。BbSre1的转录活性和核导入在ΔBbOhmm中受到抑制细胞并受细胞内活性氧（ROS）和氧水平的影响。这些发现导致了一个新的模型，其中BbOhmm与可用氧结合以控制BbSre1的转录活性来影响ROS稳态，而BbSre1则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。