减少线粒体蛋白转化促进心肌细胞增殖和心脏再生
Feng Gao1,2, Tian Liang1,2, Yao Wei Lu3
1Department of Cardiology, State Key Laboratory of Transvascular Implantation Devices, Provincial Key Lab of Cardiovascular Research, Second Affiliated Hospital (F.G., T.L., L.P., X.F., X.D., T.H., F.Z., N.L., H.Y., W.Z., X.H., J.W., J.C.).
Circulation
|October 31, 2023
概括
线粒体核糖体蛋白S5 (MRPS5) 的损失增强了心肌细胞的增殖和心脏再生,改善了受伤后的心脏功能. 这涉及ATF4调节细胞运动,为心肌修复提供新的治疗点.
科学领域:
- 心脏病学
- 线粒体生物学
- 分子生物学
背景情况:
- 线粒体对心脏功能至关重要,代谢变化与心脏病有关.
- 线粒体核蛋白S5 (MRPS5) 倒置抑制线粒体翻译,导致线粒体蛋白失衡.
- 研究MRPS5对心肌细胞增殖的影响是了解心脏病机制的关键.
研究的目的:
- 研究MRPS5损失对心肌细胞增殖和心脏再生的影响.
- 阐明线粒体应激反应在心脏修复中的作用.
- 确定心肌损伤的潜在治疗点.
主要方法:
- 有删除MRPS5等位基因的小鼠接受了心肌梗塞诱导.
- 对心肌细胞的增殖,心脏再生和心脏功能进行了体内和体外评估.
- 分子分析包括基因表达,蛋白质水平和线粒体功能测试.
主要成果:
- 在心肌梗塞后改善了心脏功能和再生.
- 确定ATF4是线粒体应激反应的关键调节剂,通过Knl1促进心肌细胞增殖.
- 抑制MRPS5或多西环林治疗增加了人类iPSC衍生的心肌细胞的增殖.
结论:
- 在心肌细胞功能和心脏修复中,MRPS5和ATF4起着至关重要的作用.
- 针对MRPS5/ATF4通路提供了心肌损伤的新疗法.
- 这项研究为开发心脏病治疗开辟了新的途径.
相关概念视频
01:13Formation of Muscle Fibers from Myoblasts
4.9K
De novo myogenesis, or the formation of muscle fibers, begins during the early embryonic stages. The skeletal muscle is formed from somites– blocks of embryonic cell layers. The somites are further divided into dermatomes, myotomes, sclerotomes, and syndetomes. Among these, the myotomes give rise to muscle fibers.
Muscle progenitor cells (MPCs) are formed from the myotomes. MPCs express genes that encode the transcription factors Pax3 and Pax7. Along with Pax 3/7, other transcription...
Muscle progenitor cells (MPCs) are formed from the myotomes. MPCs express genes that encode the transcription factors Pax3 and Pax7. Along with Pax 3/7, other transcription...
4.9K
01:21Myocarditis I: Introduction
9
Myocarditis is inflammation of the myocardium, which is the muscular layer of the heart.EtiologyMyocarditis has a diverse etiology, including a wide range of infectious and non-infectious causes:Infectious CausesViral: Common viruses include Coxsackie A and B, adenovirus, parvovirus B19, enteroviruses, and influenza A.Bacterial: Examples include infections caused by Streptococcus, Staphylococcus, and Mycoplasma species.Rickettsial: Infections like Rocky Mountain spotted fever can result in...
9
01:19Translocation of Proteins into the Mitochondria
3.1K
Mitochondrial precursors are translocated to the internal subcompartments via independent mechanisms involving distinct protein machineries called translocases.
Sorting of outer membrane proteins:
Mitochondrial outer membrane proteins are of two types: the transmembrane, beta-barrel porins, and the membrane-anchored, alpha-helical proteins. Beta-barrel porin precursors are translocated by the TOM complex and inserted into the outer mitochondrial membrane by the SAM complex. In contrast,...
Sorting of outer membrane proteins:
Mitochondrial outer membrane proteins are of two types: the transmembrane, beta-barrel porins, and the membrane-anchored, alpha-helical proteins. Beta-barrel porin precursors are translocated by the TOM complex and inserted into the outer mitochondrial membrane by the SAM complex. In contrast,...
3.1K