PLAAT1表达触发了线粒体的碎片化,这种碎片化方式取决于酶活性
Mohammad Mamun Sikder1, Toru Uyama1, Sumire Sasaki1
1Department of Biochemistry, Kagawa University School of Medicine, 1750-1 Ikenobe, Miki, Kagawa 761-0793, Japan.
Journal of biochemistry
|October 11, 2023
概括
脂酶A和转移酶1 (PLAAT1) 的过度表达改变了线粒体的形状,导致了碎片化. 这表明PLAAT1在调节线粒体生物发生和过氧体水平方面发挥了新的作用.
科学领域:
- 生物化学 生化学
- 细胞生物学 细胞生物学
- 分子生物学分子生物学
背景情况:
- 脂酶A和酸转移酶 (PLAAT) 蛋白家族包括五个成员 (PLAAT1-5) 参与脂代谢.
- 以前的研究表明,PLAAT3的过度表达导致哺乳动物细胞中的过氧体消失.
研究的目的:
- 研究PLAAT1对细胞器官的潜在影响,以PLAAT3.3的先前发现为基础.
- 阐明PLAAT1的催化活性在细胞形态学中的作用.
主要方法:
- 生成的HEK293细胞具有多西环素诱导的小鼠PLAAT1表达.
- 在PLAAT1过度表达时分析了线粒体形态和碎片化.
- 评估了线粒体分裂/融合调节器 (DRP1,OPA1,MFN2) 和有机体标记物的蛋白质水平.
主要成果:
- 过度表达PLAAT1诱导线粒体从棒形转变为圆形,并导致碎片化.
- 催化不活跃的PLAAT1突变并没有诱导线粒体形态变化,突出了酶活性的作用.
- PLAAT1表达减少了过氧体,但没有显著影响ER,戈尔吉或溶酶体标志物.
- 在PLAAT1表达细胞中观察到DRP1 (裂变) 的水平增加和OPA1和MFN2 (融合) 的水平降低.
结论:
- 在诱导线粒体形态变化方面,PLAAT1的催化活性至关重要.
- 通过促进裂变和抑制融合,PLAAT1影响线粒体动态.
- 这些发现表明,PLAAT1在线粒体生物发生和过氧体平衡中起着新的调节作用.
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
ATP Synthase: Mechanism
14.7K
In animals, the mitochondrial F1F0 ATP synthase is the key protein that synthesizes ATP molecules through a complex catalytic mechanism. While the nuclear genome encodes the majority of ATP synthase subunits, the mitochondrial genome encodes some of the enzyme's most critical components. The formation of this multi-subunit enzyme is a complex multi-step process regulated at the level of transcription, translation, and assembly. Defects in one or more of these steps can result in decreased...
14.7K
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
Mitochondrial Precursor Proteins
2.6K
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...
2.6K
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
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


