向线粒体酸酶PGAM5通过调节NRF2-介导的FSP1表达来缓解铁和急性胰腺炎
Shuang Ma1, Jianhua Qin1, Jing Luan1
1The HIT Center for Life Sciences, School of Life Science and Technology, Harbin Institute of Technology, Harbin, China.
Cell death & disease
|February 21, 2026
概括
糖酸突变酶5 (PGAM5) 调节细胞死亡途径铁亡. 调节PGAM5通过升调保护性蛋白质来保护细胞,为急性胰腺炎等疾病提供潜在的治疗策略.
科学领域:
- 细胞生物学 细胞生物学
- 生物化学 生物化学
- 病理学 病理学 病理学
背景情况:
- 铁亡是一种依赖于铁的亡,涉及脂质过氧化.
- 糖酸突变酶5 (PGAM5) 是一个调节动力学和压力的线粒体枢纽.
- 之前,PGAM5在铁亡中的作用尚不清楚.
研究的目的:
- 阐明PGAM5在铁亡中的作用.
- 研究PGAM5影响铁亡的分子机制.
- 探索在急性胰腺炎中准PGAM5的治疗潜力.
主要方法:
- 基因删除和PGAM5的过度表达.
- 核因素红色素2相关因子2 (NRF2) 和铁灭抑制蛋白1 (FSP1) 表达的分析.
- 测量细胞能量压力和AMP激活蛋白激酶 (AMPK) 激活.
- 在急性胰腺炎模型中对PGAM5的药理抑制.
主要成果:
- 由于PGAM5失调,通过调节NRF2-介导的FSP1表达来保护铁.
- 调节PGAM5会增加AMP/ATP的比率,从而激活AMPK.
- AMPK激活促进NRF2核积累和FSP1转录.
- 药理性PGAM5抑制降低了阿金诱导的急性胰腺炎的严重程度.
结论:
- PGAM5是铁灭的关键调节者.
- 通过AMPK激活,PGAM5通过NRF2/FSP1通路影响细胞存活.
- 向PGAM5显示了急性胰腺炎的治疗前景.
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