双局部的PPTC7通过与BNIP3和NIX的近位和动态相互作用来限制线粒
Lianjie Wei1, Mehmet Oguz Gok2, Jordyn D Svoboda1
1Department of Biochemistry & Molecular Biophysics, Washington University School of Medicine in St. Louis, St. Louis, MO, USA.
Life science alliance
|July 11, 2024
概括
蛋白酸酶7 (PPTC7) 通过促进BNIP3和NIX蛋白的循环,调节线粒细胞衰变. 这种线粒体酸酶针对这些蛋白质进行蛋白质体降解,控制基底线粒体的水平.
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:
- 线粒体是维护线粒体平衡的关键细胞过程.
- BNIP3和NIX是调解线粒的关键蛋白质.
- 通过PPTC7调节线粒的确切机制尚未完全理解.
研究的目的:
- 阐明PPTC7抑制BNIP3和NIX介导的线粒细胞衰变的分子机制.
- 研究PPTC7在BNIP3和NIX的转录后调节中的作用.
- 确定PPTC7在线调节中的亚细胞局部化和功能相关性.
主要方法:
- 西方涂抹测试以评估蛋白质水平和半衰期.
- 蛋白质体抑制试验.
- 对PPTC7的过度表达和局部化研究.
- 近距离标记和同定位实验.
主要成果:
- PPTC7的损失导致BNIP3和NIX的转录后上调.
- PPTC7促进了BNIP3和NIX的无处不在中介的营业额.
- 调节BNIP3和NIX水平需要PPTC7的催化活性,但线粒体局部化并不重要.
- PPTC7是双局部到外层线粒体膜和矩阵.
- 将PPTC7固定在线粒体外膜上有效地减少了BNIP3和NIX的积累.
- PPTC7与BNIP3和NIX具有动态关联. PPTC7与BNIP3和NIX具有动态关联.
结论:
- PPTC7在线粒体外中起作用,促进BNIP3和NIX的蛋白质体循环.
- 这种PPTC7的作用限制了基底线粒.
- 通过向蛋白质降解,PPTC7作为线粒细胞衰变的关键调节者.
相关概念视频
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
01:39Mitochondrial 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
01:36Delivery Pathways to the Lysosome
6.2K
Eukaryotic cells use different mechanisms to eliminate toxic waste obsolete and worn-out substances. Lysosomes play a pivotal role in this, and hence, these substances are carried to the lysosome from other parts of the cell and extracellular space through different pathways. The most elaborately studied pathways to the lysosome are the endocytic pathways.
Endocytosis
In endocytosis, the cell membrane takes up macromolecules and particles from the surrounding medium. Clathrin-mediated...
Endocytosis
In endocytosis, the cell membrane takes up macromolecules and particles from the surrounding medium. Clathrin-mediated...
6.2K
01:45Regulation of Nuclear Protein Sorting
2.4K
Nuclear protein sorting regulates nucleus composition and gene expression, crucial for determining the fate of a eukaryotic cell. Hence, the entry and exit of molecules across the nuclear envelope is a tightly controlled process. Nuclear protein sorting can be inhibited by one of the following ways: 1) masking cargo signal sequences, 2) modifying the nuclear receptor's affinity for cargo, 3) controlling the nuclear pore size, 4) retaining the cargo during its transit to the cytosol or the...
2.4K
02:04Covalently Linked Protein Regulators
6.8K
Proteins can undergo many types of post-translational modifications, often in response to changes in their environment. These modifications play an important role in the function and stability of these proteins. Covalently linked molecules include functional groups, such as methyl, acetyl, and phosphate groups, and also small proteins, such as ubiquitin. There are around 200 different types of covalent regulators that have been identified.
These groups modify specific amino acids in a protein....
These groups modify specific amino acids in a protein....
6.8K
02:23Abnormal Proliferation
4.5K
Under normal conditions, most adult cells remain in a non-proliferative state unless stimulated by internal or external factors to replace lost cells. Abnormal cell proliferation is a condition in which the cell's growth exceeds and is uncoordinated with normal cells. In such situations, cell division persists in the same excessive manner even after cessation of the stimuli, leading to persistent tumors. The tumor arises from the damaged cells that replicate to pass the damage to the...
4.5K