通过调节DRP1功能,PGAM5裂变和寡合化平衡了压力下的线粒体动力学
Sudeshna Nag1, Kaitlin Szederkenyi1,2, Christopher M Yip1,2
1Department of Biochemistry, University of Toronto, MaRS Centre West Tower, 661 University Ave., M5G 1M1, Toronto, Canada.
Journal of cell science
|October 9, 2025
概括
糖酸突变酶5 (PGAM5) 蛋白活性由其寡合化和裂变来调节. 这些事件控制PGAM5.
科学领域:
- 线粒体生物学和细胞动力学.
- 蛋白质调节和翻译后的修改.
背景情况:
- 线粒体动力学由动胺GTPases,如线粒素1 (MFN1),线粒素2 (MFN2) 和动胺相关蛋白1 (DRP1) 控制.
- 糖酸突变酶5 (PGAM5) 影响MFN2和DRP1的酸化和功能,但其调节机制尚不清楚.
研究的目的:
- 为了阐明糖酸突变酶5 (PGAM5) 活性的精确调节.
- 研究PGAM5寡合化和局部化在控制线粒体动态中的作用.
主要方法:
- 在细胞应激条件下的PGAM5寡合化状态 (dodecamer与dimer) 的分析.
- 评估PGAM5与MFN2和DRP1.1的差异性结合亲和力.
- 通过内部线粒体蛋白酶PARL和OMA1.1对PGAM5裂变的研究.
- 追踪PGAM5转移到细胞分裂后的细胞质.
主要成果:
- 在脱极化和代谢压力下,PGAM5从十二相转变为二相.
- 与十二相相相比,PGAM5二相对MFN2和DRP1具有改变的亲和力.
- PGAM5通过PARL和OMA1进行裂变,其中一部分转移到细胞质中.
结论:
- PGAM5的寡合化状态 (dodecamer与dimer) 是其功能的一个关键调节器.
- 裂变引起的PGAM5转移到细胞质中进一步调节其活性.
- 这些调节事件对于控制细胞压力期间的线粒体动力学至关重要.
相关概念视频
Mitochondrial Membranes
16.6K
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,...
16.6K
Translocation of Proteins into the Mitochondria
12.2K
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,...
12.2K
Porin Insertion in the Outer Mitochondrial Membrane
4.6K
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...
4.6K
Mitochondrial Protein Sorting
5.6K
Mitochondria are double-membrane organelles of the eukaryotes involved in cellular metabolism, signaling, ATP synthesis, and programmed cell death. Each of these processes requires specific proteins and enzymes that must be correctly sorted to the right mitochondrial subcompartment for the proper functioning of the organelle.
Most of these mitochondrial proteins are encoded by the nucleus and imported to the mitochondria as unfolded or loosely folded precursors. Mitochondrial precursors...
Most of these mitochondrial proteins are encoded by the nucleus and imported to the mitochondria as unfolded or loosely folded precursors. Mitochondrial precursors...
5.6K
Mitochondrial Precursor Proteins
3.6K
Mitochondrial precursors are partially unfolded or loosely folded polypeptide chains. Newly synthesized precursors are inhibited from spontaneously folding into their native conformation by the cytosolic chaperones, heat shock proteins 70 (Hsp70), and mitochondrial import stimulation factors (MSFs). Precursors bound to MSFs are guided to the TOM70-TOM37 receptors, while precursors bound to Hsp70 chaperones are targetted to TOM20-TOM22 receptor complexes.
Most of the mitochondrial...
Most of the mitochondrial...
3.6K
Structure of Porins
3.8K
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...
3.8K


