多年财政框架的SUMOylation协调裂变复合体,以促进压力诱导的线粒体分裂
Richard Seager1, Nitheyaa Shree Ramesh1, Stephen Cross2
1School of Biochemistry, University of Bristol, Biomedical Sciences Building, Bristol BS8 1TD, UK.
Science advances
|October 4, 2024
概括
在压力期间的线粒体碎片化受到MFF SUMOylation的调节,这是AMPK增强的过程. 这种SUMOylation控制了MiD结合,影响了DRP1复合体的形成和线粒体动态.
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
- 分子机制的分子机制
背景情况:
- 线粒体碎片化对于细胞对生物能压力的反应至关重要.
- 动氨酸相关蛋白1 (DRP1) 通过对线粒体的招募来调解裂变.
- 线粒体裂变因子 (MFF) 和MiD49/51是形成裂变复合物的关键DRP1受体.
研究的目的:
- 阐明将AMPK介导的MFF酸化与线粒体碎片化的分子机制.
- 研究SUMOylation在调节MFF功能和线粒体动态中的作用.
主要方法:
- 多年财政框架的SUMOylation站点的识别 (Lys151).
- 在AMPK激活和线粒体应激 (CCCP) 下对MFFSUMOylation和MiD结合的分析.
- 在表达野生类型的MFF-knockout细胞与非SUMOylatableMFF (K151R) 中评估线粒体碎片化.
主要成果:
- 在Lys151中,MFF被SUMOylated,并且通过AMPK介导的酸化来增强这种修饰.
- 多年财政预算的SUMOylation调节了MiD蛋白与多年财政预算的结合.
- 线粒体应激 (CCCP) 增加了MFF SUMOylation,并促进了碎片化,而在MFF K151R突变中,这种碎片化受损.
结论:
- AMPK-MFF SUMOylation轴是压力诱导的线粒体分裂的关键调节器.
- 多基的SUMOylation可以动态控制三裂变复合体内的MiD水平.
- 这一途径为理解和潜在地调节线粒体动态提供了一个新的目标.
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
Mitochondrial Protein Sorting
4.3K
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...
4.3K
Disassembly of Intermediate Filaments
2.0K
Intermediate filaments (IFs) do not undergo spontaneous disassembly. Enzymes, kinases, and phosphatases add and remove phosphates from specific sites to regulate their disassembly. The IF concentration in the cytoplasm also regulates the disassembly. If the concentration crosses a threshold, it activates the protein kinases in the vicinity, allowing the phosphorylation of IFs.
Keratin proteins, found at the cell periphery near cell junctions, undergo a cycle of assembly and disassembly. In Type...
Keratin proteins, found at the cell periphery near cell junctions, undergo a cycle of assembly and disassembly. In Type...
2.0K
Mitochondrial Precursor Proteins
2.5K
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...
2.5K
Destabilization of Microtubules
2.6K
The destabilization of microtubules can occur during different stages of the microtubule lifecycle, such as nucleation or elongation. It can take place at either end of the microtubule or in the microtubule lattices as a whole. The lifespan of individual microtubules within a cell varies according to the cell type and stage of the cell cycle. During interphase, the lifespan of the microtubule is about 30 minutes, while during cell division, it is about 15 minutes. In axonal microtubules of...
2.6K
Mitochondrial Membranes
9.1K
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,...
9.1K


