尼克斯与WIPI2相互作用,诱导线粒的发生
Eric N Bunker1, François Le Guerroué1, Chunxin Wang1
1Surgical Neurology Branch, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD, USA.
The EMBO journal
|August 25, 2023
概括
尼克斯蛋白通过其最小基本区域 (MER) 与WIPI2相互作用,并通过其LC3相互作用 (LIR) 动机与ATG8蛋白相互作用,从而启动甲基. 这两种相互作用对于有效的线粒细胞吸收是至关重要的.
科学领域:
- 细胞生物学 细胞生物学
- 分子生物学分子生物学
- 自学研究 自学研究
背景情况:
- 尼克斯是一种外层线粒体蛋白质,可触发自的选择性形式 - - 线粒体细胞分裂.
- 尼克斯具有用于ATG8结合的LC3相互作用 (LIR) 基因以及在线粒中未定义作用的最小基本区域 (MER).
- 尼克斯诱导线粒的确切机制,特别是其MER的功能,仍然在很大程度上是未知的.
研究的目的:
- 阐明尼克斯介导的线粒的机制,重点关注LIR动机和MER的作用.
- 为了研究Nix在线诱导过程中如何与其他与自相关的蛋白质相互作用.
- 了解独立于正规启动复合体的尼克斯诱导线粒的上游事件.
主要方法:
- 使用化学诱导二分化 (CID) 来剖析尼克斯的LIR动机和MER的功能.
- 研究了Nix,WIPI2和ATG8蛋白之间的蛋白质-蛋白质相互作用.
- 分析了WIPI2的亚细胞局部化,以应对Nix及其域.
主要成果:
- 尼克斯的LIR动机和MER都对强大的线粒是必不可少的.
- 尼克斯MER直接与自效应器WIPI2相互作用并将其招募到线粒体中.
- 尼克斯LIR图案是将均的WIPI2分布转换为puncta所必需的,即使没有ATG8蛋白.
结论:
- 尼克斯诱导的线粒包括一种新的机制,即MER招募WIPI2,而LIR动机进一步组织WIPI2.
- 这项研究揭示了Nix MER在启动线粒的难以捉摸的功能.
- 尼克斯提供了一个自诱导的例子,该诱导作用于正规启动复合体的下游,突出了自调节的替代途径.
相关概念视频
Translocation of Proteins into the Mitochondria
3.2K
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,...
3.2K
Mitochondrial Protein Sorting
4.4K
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...
4.4K
Autophagic Cell Death
3.4K
Christian de Duve discovered “autophagy,” a process in which cellular components are engulfed by membrane-bound organelles called autophagosomes. The autophagosomes then fuse with lysosomes to digest the enclosed contents. Autophagy is generally activated in cells to prevent cell death. However, cell death is triggered when the damage is beyond repair.
Autophagy and Apoptosis
Autophagy can activate apoptosis. In normal conditions, the autophagy activating protein Beclin-1 and...
Autophagy and Apoptosis
Autophagy can activate apoptosis. In normal conditions, the autophagy activating protein Beclin-1 and...
3.4K
Delivery Pathways to the Lysosome
6.6K
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...
6.6K
Necrosis
4.6K
Necrosis is considered as an “accidental” or unexpected form of cell death that ends in cell lysis. The first noticeable mention of “necrosis” was in 1859 when Rudolf Virchow used this term to describe advanced tissue breakdown in his compilation titled “Cell Pathology”.
Morphological Manifestations of Necrosis
Necrotic cells show different types of morphological appearance depending on the type of tissue and infection. In coagulative necrosis, cells become...
Morphological Manifestations of Necrosis
Necrotic cells show different types of morphological appearance depending on the type of tissue and infection. In coagulative necrosis, cells become...
4.6K
The Intrinsic Apoptotic Pathway
6.6K
Internal cellular stress, such as cellular injury or hypoxia, triggers intrinsic apoptosis. The B-cell lymphoma 2 (Bcl-2) family of proteins are the primary regulators of the intrinsic apoptotic pathway. For example, during DNA damage, checkpoint proteins, such as Ataxia Telangiectasia Mutated (ATM protein) and Checkpoints Factor-2 (Chk2) proteins, are activated. These proteins phosphorylate p53 which further activates pro-apoptotic proteins, such as Bax, Bak, PUMA, and Noxa, and inhibits...
6.6K


