Amahisa Madoka, Tsukagoshi Madoka, Kadooka Chihiro, Masuo Shunsuke, Takeshita Norio, Doi Yuki, Takagi Hiroshi, Takaya Naoki
Microbiology Research Center for Sustainability, Faculty of Life and Environmental Sciences, University of Tsukuba, 1-1-1 Tennodai, Tsukuba 305-8572, Japan.
Institute for Research Initiatives, Nara Institute of Science and Technology, 8916-5 Takayama, Ikoma 630-0192, Japan.
J Fungi (Basel). 2024 Jan 10;10(1):58. doi: 10.3390/jof10010058.
Nitric oxide (NO) is a natural reactive nitrogen species (RNS) that alters proteins, DNA, and lipids and damages biological activities. Although microorganisms respond to and detoxify NO, the regulation of the cellular metabolic mechanisms that cause cells to tolerate RNS toxicity is not completely understood. We found that the proline and arginine auxotrophic and mutants of the fungus require more arginine and proline for normal growth under RNS stress that starves cells by accumulating fewer amino acids. Fungal transcriptomes indicated that RNS stress upregulates the expression of the biosynthetic genes required for global amino acids, including proline and arginine. A mutant of the gene disruptant, , which encodes the transcriptional regulation of the cross-pathway control of general amino acid synthesis, did not induce these genes, and cells accumulated fewer amino acids under RNS stress. These results indicated a novel function of CpcA in the cellular response to RNS stress, which is mediated through amino acid starvation and induces the transcription of genes for general amino acid synthesis. Since CpcA also controls organic acid biosynthesis, impaired intermediates of such biosynthesis might starve cells of amino acids. These findings revealed the importance of the mechanism regulating amino acid homeostasis for fungal responses to and survival under RNS stress.
一氧化氮（NO）是一种天然的活性氮物质（RNS），它会改变蛋白质、DNA和脂质，并损害生物活性。尽管微生物会对NO做出反应并进行解毒，但导致细胞耐受RNS毒性的细胞代谢机制的调节尚未完全了解。我们发现，脯氨酸和精氨酸营养缺陷型真菌突变体在RNS胁迫下正常生长需要更多的精氨酸和脯氨酸，RNS胁迫会通过减少氨基酸积累使细胞饥饿。真菌转录组表明，RNS胁迫会上调包括脯氨酸和精氨酸在内的全局氨基酸生物合成基因的表达。编码一般氨基酸合成的交叉途径控制转录调控的基因破坏突变体，不会诱导这些基因，并且细胞在RNS胁迫下积累的氨基酸较少。这些结果表明CpcA在细胞对RNS胁迫的反应中具有新功能，这是通过氨基酸饥饿介导的，并诱导一般氨基酸合成基因的转录。由于CpcA还控制有机酸生物合成，这种生物合成的受损中间产物可能会使细胞缺乏氨基酸。这些发现揭示了调节氨基酸稳态的机制对于真菌在RNS胁迫下的反应和存活的重要性。
