激活转录因子4调节线粒体含量,形态和功能,在骨肌肉髓管区分方面发挥作用
Jonathan M Memme1, Victoria C Sanfrancesco1, David A Hood1
1Muscle Health Research Centre, School of Kinesiology and Health Science, York University, Toronto, Ontario, Canada.
American journal of physiology. Cell physiology
|June 5, 2023
概括
激活转录因子4 (ATF4) 对于肌肉细胞分化和线粒体质量控制至关重要. ATF4促进线粒体健康和适应压力,增强功能和减少肌肉细胞的损伤.
科学领域:
- 肌肉生理学 肌肉生理学
- 线粒体生物学 线粒体生物学
- 细胞应激反应的细胞应激反应
背景情况:
- 线粒体功能对健康至关重要,线粒体展开的蛋白质反应 (UPRmt) 调节压力下的平衡.
- 在肌肉线粒体质量控制 (MQC) 中激活转录因子4 (ATF4) 的作用尚不清楚.
研究的目的:
- 研究ATF4在调节MQC和C2C12神经管中在分化和收缩活动期间适应的必要性和充分性.
主要方法:
- 在C2C12神经细胞中,ATF4的过度表达 (OE) 和敲除.
- 分化为肌管和暴露于急性 (ACA) 和慢性 (CCA) 收缩活动.
- 对肌源性因素,线粒体生物发生,融合,UPRmt激活和自的分析.
主要成果:
- ATF4通过Myc和MyoD调解髓管形成,抑制基底线粒体生物发生 (PGC-1α).
- ATF4与线粒体融合,UPRmt激活,溶酶体生物发生和自相关.
- ATF4促进了高功能线粒体的网络,增加了氧气消耗和减少了反应性氧物种.
结论:
- 在分化和收缩活动期间,ATF4对于MQC和肌肉细胞的适应是必要和充分的.
- 在肌肉中,ATF4调节线粒体形态,溶酶体生物发生和线粒体细胞衰变.
- 这些发现扩大了ATF4已知的功能,超越了规范的角色,包括线粒体动力学和肌肉质量控制.
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