血清蛋白合成控制了巨细胞中线粒体生物发生的过程
Chuanlong Wang1,2, Muyang Zhao1, Peng Bin1
1State Key Laboratory of Swine and Poultry Breeding Industry, College of Animal Science, South China Agricultural University, Guangzhou 510642, China.
Science advances
|May 17, 2024
概括
糖酸脱酶 (PHGDH) 缺乏通过促进线粒体活性氧物种 (mtROS) 来增强线粒体生物发生. 这一发现为炎症性和线粒体介导疾病提供了一个新的治疗点.
科学领域:
- 生物化学 生物化学
- 细胞生物学 细胞生物学
- 免疫学 免疫学 免疫学
背景情况:
- 线粒体功能障碍是炎症性疾病的核心.
- 针对线粒体生物生成可以改善这种功能障碍.
- 糖酸脱酶在炎症中的作用尚不清楚.
研究的目的:
- 研究PHGDH在线粒体生物发生和炎症性疾病中的作用.
- 阐明PHGDH影响线粒体功能的机制.
- 探索PHGDH作为炎症状况的治疗点.
主要方法:
- 研究了巨细胞中的PHGDH缺乏.
- 评估了线粒体生物发生的标记物.
- 测量了线粒体反应性氧物种 (mtROS) 生产.
- 分析了下游的信号通路,包括HIF-1α,Nsp1和Nrf1.1.
- 在饮食诱导的肥胖模型中研究了骨髓质Phgdh缺乏的影响.
主要成果:
- 发现PHGDH缺乏会在炎症性巨细胞中促进线粒体生物发生.
- 缺少PHGDH会通过抑制谷氨酸的合成来增加mtROS.
- mtROS信号激活了HIF-1α,NSP1和Nrf1的转录.
- 骨髓细胞Phgdh缺乏逆转了饮食引起的肥胖.
- 鉴定出新的血清蛋白合成是线粒体生物发生的关键调节者.
结论:
- 缺少PHGDH可以通过mtROS和随后的信号传递促进线粒体生物发生.
- 这一途径涉及线粒体与核之间的通信.
- 在炎症性和线粒体介导疾病中,PHGDH是潜在的治疗点.
- 针对de novo血清合成可能是一个新的治疗策略.
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