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Updated: Jun 24, 2025

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PNPO-PLP轴通过调节 lysosomal 活动来感知长时间的巨细胞缺氧

Hiroki Sekine¹, Haruna Takeda², Norihiko Takeda^3,4

¹Department of Medical Biochemistry, Tohoku University Graduate School of Medicine, Sendai, Japan. hiroki.sekine.c2@tohoku.ac.jp.

Nature metabolism

|May 31, 2024

概括

氨酸5'-酸氧化酶 (PNPO) 作为氧气传感器,在长时间的低氧期间调节巨细胞溶解体活性. 这一途径影响维生素B6的新陈代谢,导致炎症和延迟解决.

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:

氧气对超生物生命至关重要,影响生理和病理过程.
虽然急性缺氧反应是可以理解的,但长期缺氧的机制仍然不清楚.
溶解体功能和炎症反应在疾病发病过程中至关重要.

研究的目的:

在长期缺氧中识别新的氧气感应机制.
阐明素5'-酸盐氧化酶 (PNPO) 在氧气传感中的作用.
为了研究缺氧对 lysosomal 活动和巨细胞功能的影响.

主要方法:

在不同氧度下研究PNPO活性.
评估维生素B6活性形式的含量,特别是氧化5'-酸盐 (PLP).
分析了溶酶体酸化,铁失调,TET2蛋白水平和巨细胞中的炎症标志物.

主要成果:

长时间的缺氧会降低PNPO活性,降低PLP水平.
抑制了 lysosomal 酸化和抑制了超硫化物合成.
观察到铁的调节失调,TET2蛋白质的损失,以及巨细胞中炎症分辨率的延迟.
确定PNPO-PLP轴作为一种新的氧气传感途径.

结论:

PNPO作为氧气传感器起作用,将长期低氧与抑制的PLP依赖代谢联系起来.
这导致溶酶体功能障碍和亲炎性巨细胞表型.
PNPO-PLP轴代表了一个独特的氧气感应层,影响细胞代谢和炎症.

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Lysosomal Hydrolases

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Lysosomes are the site for the degradation of macromolecules and biological polymers released during membrane trafficking events such as secretory, endocytic, autophagic, and phagocytic pathways. The membrane-enclosed area of the lysosome, called the lumen, contains hydrolytic enzymes active in an acidic environment. These acid hydrolases are functional at a pH between 4.5 and 5 and are involved in cellular processes such as cell signaling, energy metabolism, restoration of the plasma membrane,...