人类Fis1以一种进化保守的方式直接与DRp1相互作用,促进线粒体裂变
Kelsey A Nolden1, Megan C Harwig1, R Blake Hill1
1Department of Biochemistry, Medical College of Wisconsin, Milwaukee, Wisconsin, USA.
The Journal of biological chemistry
|October 22, 2023
概括
人类Fis1直接与人类Drp1相互作用,调节线粒体分裂. 这种受Fis1结构特征控制的保守相互作用,会影响人类细胞中的线粒体形态学.
科学领域:
- 细胞生物学 细胞生物学
- 分子生物学分子生物学
- 生物化学 生物化学
背景情况:
- 线粒体分裂对细胞功能至关重要,并依赖于保存的蛋白质.
- 线粒体裂变蛋白1 (Fis1) 和胺相关蛋白1 (Drp1) 是这个过程中的关键参与者.
- 虽然Fis1和Drp1在酵母中相互作用,但它们在更高的真核生物中保持的直接相互作用尚未完全理解.
研究的目的:
- 调查人类Fis1和人类Drp1.1之间的直接相互作用.
- 阐明人类细胞中Fis1-Drp1相互作用的结构基础和功能后果.
- 为了确定Fis1-Drp1相互作用机制是否在真核生物中保持.
主要方法:
- 核磁共振 (NMR) 光谱学 核磁共振 (NMR) 光谱学
- 差分扫描光测量 (DSF) 是一种
- 微尺度热泳 (MST) 是一种
- 氨酸扫描突变的突变发生.
主要成果:
- 人类Fis1直接结合人类Drp1 (KD=12-68μM),抑制Drp1的组合,但不能抑制GTP的水解.
- Fis1的N端臂和一个保留的表面对于Fis1-Drp1相互作用至关重要.
- 在Fis1 (例如,E7A,Y76A) 中的突变深刻地改变了线粒体形态,导致碎片化或延长.
- 在Fis1内部的分子内相互作用,类似于酵母,促进Drp1介导的裂变.
结论:
- 直接的Fis1-Drp1相互作用在人体中保留,在调节线粒体分裂方面发挥着重要作用.
- 通过与Drp1.1的相互作用,Fis1充当线粒体形态的关键调节者.
- 这些发现突出了整个真核生物进化过程中线粒体动态的保存机制.
相关概念视频
Translocation 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
Energy to Drive Translocation
2.1K
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...
2.1K
Porin Insertion in the Outer Mitochondrial Membrane
3.0K
Porins are beta-barrel proteins translocated to the mitochondrial outer membrane through the TOM complex into the intermembrane space. Porin precursors bind TIM chaperones within the intermembrane space and are guided to the Sorting and Assembly Machinery complex or SAM complex on the outer mitochondrial membrane.
Three models describe the assembly of porins by the SAM complex and their insertion into the outer membrane. Model 1 suggests that porins are assembled outside the SAM channel as the...
Three models describe the assembly of porins by the SAM complex and their insertion into the outer membrane. Model 1 suggests that porins are assembled outside the SAM channel as the...
3.0K
The Inner Mitochondrial Membrane
3.4K
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...
3.4K
Structure of Porins
3.0K
Mitochondria, chloroplasts, and gram-negative bacteria have transmembrane, beta-barrel proteins called porins to mediate the free diffusion of ions and metabolites across the membrane. Mitochondrial porin precursors contain conserved amino acid sequences called beta signals at their C-terminal. Beta signals have a motif of PoXGXXHyXHy (Po-Polar, X-Any amino acid, G-Glycine, Hy-LargeHydrophobic), which are crucial for precursor recognition to initiate precursor assembly. Beta-barrel...
3.0K
Mitochondrial Membranes
11.3K
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,...
11.3K


