在细胞周期期间,需要MIRO1来动态增加线粒体-ER接触点和线粒体ATP
Benney T Endoni1,2, Olha M Koval1, Chantal Allamargot3
1Abboud Cardiovascular Research Center, Division of Cardiovascular Medicine, Department of Internal Medicine, Carver College of Medicine, University of Iowa, Iowa City, IA 52242, USA.
Cells
|April 11, 2025
概括
线粒体-ER接触点 (MERCS) 在细胞周期期间增加,由MIRO1.1驱动. 这增强了线粒体,新陈代谢和细胞增殖.
科学领域:
- 细胞生物学 细胞生物学
- 线粒体生物学 线粒体生物学
- 细胞循环规则 细胞循环规则
背景情况:
- 线粒体-ER接触点 (MERCS) 对于细胞功能至关重要,包括 (Ca2+) 稳态和能量代谢.
- 外部线粒体蛋白质线粒体rho GTPase 1 (MIRO1) 与线粒体动力学有关,但其在细胞周期依赖的MERCS中的作用尚不清楚.
研究的目的:
- 调查细胞周期期间线粒体代谢的变化是否依赖于MERCS动态.
- 确定MIRO1在细胞周期依赖的MERCS和线粒体功能中的调节作用.
主要方法:
- 在小鼠中,MIRO1的纤维细胞特异性删除和随后的伤口愈合的评估.
- 评估野生型和MIRO1缺乏纤维细胞和血管光滑肌细胞的增殖,细胞循环进展,MERCS数量和蛋白质组成.
- 使用生物化学和光技术分析Ca2+过渡物,线粒体代谢和ATP水平.
- 缺乏特定域的MIRO1突变的功能评估.
主要成果:
- 在细胞周期的G1/S阶段,MERCS数量和接近度增加,与线粒体Ca2+升高,膜潜力和ATP水平相关.
- MIRO1 缺陷取消了细胞循环进展 (G1/S),MERCS 形成,并改变了 ER 和线粒体之间的 Ca2+ 处理.
- 缺乏EF手或跨膜域的MIRO1突变未能挽救扩散或MERCS形成.
结论:
- MIRO1对于细胞周期依赖MERCS的增加至关重要.
- MIRO1利用其EF手调节线粒体Ca2+吸收,从而驱动代谢活动和增殖.
- 由MIRO1调节的MERCS动态对于协调线粒体功能与细胞周期进展至关重要.
相关概念视频
01:19Translocation of Proteins into the Mitochondria
3.0K
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,...
3.0K
01:28The Inner Mitochondrial Membrane
3.2K
The inner mitochondrial membrane is the primary site of ATP synthesis. The inner membrane domain that forms a smooth layer adjacent to the outer membrane is called the inner boundary membrane. This domain contains membrane transporters that drive metabolites in and out of the mitochondria. In contrast, the inner membrane network that invaginates into the matrix space is called the cristae membrane. This domain accounts for principle mitochondrial function as it accommodates the protein...
3.2K
02:15M-Cdk Drives Transition Into Mitosis
5.5K
Checkpoints throughout the cell cycle serve as safeguards and gatekeepers, allowing the cell cycle to progress in favorable conditions and slow or halt it in problematic ones. This regulation is known as the cell cycle control system.
Cyclin-dependent kinases, or Cdks, work in concert with cyclins to control cell cycle transitions. M-Cdk, a complex of Cdk1 bound to M cyclin, is a well-known example of this coordinated control that drives the transition from the G2 to the M phase.
M cyclin...
Cyclin-dependent kinases, or Cdks, work in concert with cyclins to control cell cycle transitions. M-Cdk, a complex of Cdk1 bound to M cyclin, is a well-known example of this coordinated control that drives the transition from the G2 to the M phase.
M cyclin...
5.5K
01:45Mitochondrial Membranes
6.6K
A single mitochondrion is a bean-shaped organelle enclosed by a double-membrane system. The outer membrane of mitochondria is smooth and contains many porins - the integral membrane transporters. Porins enable free diffusion of ions and small uncharged molecules through the outer mitochondrial membrane but limit the transport of molecules larger than 5000 Daltons. Further, the outer mitochondrial membrane forms a unique structure called membrane contact sites with other subcellular organelles,...
6.6K
01:37Energy to Drive Translocation
2.0K
Mitochondrial protein import is powered by two distinct energy sources: ATP hydrolysis and electrochemical potential across the inner membrane. Newly synthesized precursors are bound by cytosolic chaperones of the Hsp70 family, which guide them to the import receptors on the mitochondrial surface. Utilizing the energy of ATP hydrolysis, Hsp70 chaperones transfer these precursors to the TOM receptors on the mitochondrial outer membrane.
Generally, polypeptides are unfolded by two distinct...
Generally, polypeptides are unfolded by two distinct...
2.0K
01:37Mitochondria
8.9K
Mitochondria are eukaryotic cellular organelles that are known to produce energy through a process called oxidative phosphorylation. Besides their primary function, mitochondria are involved in various cellular processes, including cell growth, differentiation, signaling, metabolism, and senescence. Age-related changes cause a decline in mitochondrial quality and integrity due to increased mitochondrial mutations and oxidative damage. Thus, aging can severely impact mitochondrial functions,...
8.9K