通过FSP1介导的脂质滴质量控制可以防止中性脂质过氧化和铁化
Mike Lange1,2, Michele Wölk3, Cody E Doubravsky1,2
1Department of Molecular and Cell Biology, University of California, Berkeley, Berkeley, CA 94720, USA.
bioRxiv : the preprint server for biology
|January 20, 2025
概括
铁代抑制蛋白1 (FSP1) 通过循环共酶Q10来防止脂滴中中性脂类过氧化. 功能受损的FSP1活动会导致氧化脂质和铁亡,特别是在具有多不和脂肪酸丰富脂质滴滴的癌细胞中.
科学领域:
- 细胞生物学 细胞生物学
- 生物化学 生化学
- 癌症研究 癌症研究
背景情况:
- 脂质滴 (LDs) 储存中性脂质,但它们对过氧化和保护机制的敏感性仍然不清楚.
- 已建立的途径保护膜脂,但不保护LD中的中性脂质.
研究的目的:
- 研究保护脂质滴中的中性脂质免受氧化损伤的机制.
- 为了确定中性脂质完整性和铁亡的关键调节者,以应对脂质过氧化.
主要方法:
- 利用脂管学来分析具有或没有ferroptosis抑制蛋白1 (FSP1) 的细胞中的脂质资料.
- 使用FSP1,辅酶Q10 (CoQ10) 和NADH进行了生化复制试验.
- 在不同的脂质组成下研究了癌细胞对FSP1损失的敏感性.
主要成果:
- 确定了LD局部化的FSP1作为预防中性脂质过氧化的关键调节剂.
- FSP1的损失导致氧化三糖醇和胆固醇的积累.
- 生物化学复制证明了FSP1在抑制三糖醇过氧化中的作用.
- 富含多不和脂肪酸 (PUFA) 的LD增加了癌细胞对FSP1损失的敏感性,引发了铁亡.
结论:
- 发现了第一个涉及FSP1.1的脂质滴脂质量控制途径.
- LD局部化的FSP1通过回收CoQ10来保持中性脂质完整性,防止氧化脂质的积累.
- 这一途径对于防止ferroptosis诱导至关重要,特别是在FSP1活性受损或PUFA含量高的情况下.
相关概念视频
01:16Necrosis
4.2K
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...
4.2K
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
01:26Membrane Fluidity
10.9K
Membrane fluidity is explained by the fluid mosaic model of the cell membrane, which describes the plasma membrane structure as a mosaic of components—including phospholipids, cholesterol, proteins, and carbohydrates—that gives the membrane a fluid character.
Mosaic nature of the membrane
The mosaic characteristic of the membrane helps the plasma membrane remain fluid. The integral proteins and lipids exist as separate but loosely-attached molecules in the membrane. The membrane is...
Mosaic nature of the membrane
The mosaic characteristic of the membrane helps the plasma membrane remain fluid. The integral proteins and lipids exist as separate but loosely-attached molecules in the membrane. The membrane is...
10.9K
01:24Peroxisomes
10.0K
Peroxisomes are specialized organelles present in fungi, plant, and animal cells. It can vary in number, size, morphology, and activity depending on the type of tissue and the nutritional state of the cell. For example, cells with active lipid metabolism, such as adipocytes, neurons, and hepatocytes, have more peroxisomes than other cells in the body. Besides their primary role in breaking down complex organic molecules, peroxisomes can also synthesize specific macromolecules and participate in...
10.0K