线粒体脱酶的核转位作为一种适应性心脏保护机制
Shubhi Srivastava1, Priyanka Gajwani1, Jordan Jousma2
1Department of Biochemistry and Molecular Genetics, The University of Illinois College of Medicine, Chicago, IL, USA.
Nature communications
|July 19, 2023
概括
癌症幸存者面临化学疗法诱导的心脏损伤. 一种新的适应性反应涉及线粒体酶移动到核,通过代谢物和AMPK通路保护心脏细胞.
科学领域:
- 心脏病学 心脏病学
- 分子生物学分子生物学
- 生物化学 生物化学
背景情况:
- 化疗,特别是人环素,会导致严重的心脏损伤.
- 对心肌细胞适应性反应对环素心脏毒性的机制尚不清楚.
- 线粒体损伤是化疗引起的心脏损伤的一个关键因素.
研究的目的:
- 调查心肌细胞对抗 antracycline 诱导的心脏毒性的适应机制.
- 确定参与细胞应激反应的新型保护途径.
- 探索线粒体酶在核适应中的作用.
主要方法:
- 使用人类诱导的多能干细胞衍生心肌细胞 (hiPSC-CMs).
- 进行了体内研究,以验证发现.
- 分析了线粒体三碳酸 (TCA) 循环脱酶的核转位.
- 研究了代谢物诱导的染色质可访问性和AMP-激酶 (AMPK) 信号传导.
主要成果:
- 观察到特定的线粒体TCA循环脱酶的转移到细胞核,以应对人环素.
- 证明核向脱酶在体外和体内都保持功能.
- 确定了代谢物诱导的染色体变化和AMPK信号作为关键的保护通路.
- 心肌细胞损伤程度与线粒体损伤和核适应反应之间的平衡有关.
结论:
- 线粒体脱酶的核转位是一种对抗化疗引起的心脏毒性的内生适应机制.
- 这一过程涉及代谢物介导的染色质重塑和AMPK激活.
- 针对这种核路径提供了一个潜在的策略,以减轻癌症幸存者的心脏损伤.
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