在细胞死亡启动期间减弱的生长因子信号使膜对过氧化敏感
André Gollowitzer1, Helmut Pein2, Zhigang Rao1
1Michael Popp Institute and Center for Molecular Biosciences Innsbruck (CMBI), University of Innsbruck, 6020, Innsbruck, Austria.
Nature communications
|February 25, 2025
概括
细胞毒性压力将脂肪酸重定向到细胞膜中,增加对氧化损伤的敏感性. 这发生在增长因子信号减弱时,影响细胞死亡途径,如细胞亡.
科学领域:
- 细胞生物学 细胞生物学
- 生物化学 生物化学
- 分子信号传递是分子信号传递.
背景情况:
- 细胞死亡途径如亡和铁亡涉及氧化还原稳定,脂质新陈代谢和膜完整性.
- 新出现的证据表明,这些独特的细胞死亡机制之间存在交叉对话.
研究的目的:
- 研究将细胞毒性压力,脂质代谢和细胞死亡途径联系起来的分子机制.
- 阐明受体氨酸激酶 (RTK) 信号在调节细胞对氧化膜损伤敏感性的作用.
主要方法:
- 在细胞毒性压力下分析脂质代谢和脂肪酸道化.
- 对信号通路的研究,包括RTK-PI3K-Akt-SREBP1.1.
- 对细胞死亡表型的评估,以应对遗传和药理学调制.
主要成果:
- 细胞毒性压力诱导了溶解脂酸转移酶12活性,将多不和脂肪酸引导到脂中.
- 这种重编程与改变的-CoA合成酶异酶表达和抑制的新脂肪酸生物合成有关.
- 由于RTK信号传输减少,Akt-SREBP1激活受损有利于多不和脂肪酸融入脂中,增加过氧化易感性.
- 血清饥饿模仿了这种效应,而RTK配体则抵消了这一效应.
结论:
- 在细胞死亡启动过程中减弱的RTK信号,为细胞氧化膜损伤提供了原始信号.
- 这种机制突出显示了细胞亡和替代细胞死亡程序之间的关键接口,由脂质代谢介导.
- 了解这种交叉对话,可以了解压力下细胞命运决策的调节.
更多相关视频
06:12Author Spotlight: THP-1 Macrophage Response to LPS/ATP — Unveiling the Pyroptosis, Apoptosis, and Necroptosis Spectrum
Published on: May 3, 2024
1.6K
04:01Author Spotlight: Tracing the Ferroptotic Signatures and Cell Death Dynamics in Medulloblastoma for Advanced Therapeutics
Published on: March 15, 2024
833
相关概念视频
01:17The Extrinsic Apoptotic Pathway
5.9K
The extrinsic apoptotic pathway is initiated when extracellular death-inducing signals, such as specific cytokines, activate the death receptors expressed on the cell surface. The immune cells involved in this pathway are natural killer cells (NK cells) and cytotoxic T-lymphocytes. NK cells are critical in innate immune response, while cytotoxic T-lymphocytes are associated with adaptive immune response. These cells recognize specific receptors expressed on the altered cells and activate...
5.9K
01:31The Intrinsic Apoptotic Pathway
6.0K
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...
6.0K
01:30Overview of Cell Death
6.3K
Cell death is an essential process where the body gets rid of old or damaged cells. Cell proliferation and death need to be balanced, as an imbalance between the two may lead to cancer or autoimmune diseases.
Cell death was observed in the early 19th century, but there was no experimental evidence to prove it. In 1842, Carl Vogt first discovered cell death in a metamorphic toad; however, it was not termed ‘cell death.’ Scientists discovered different cell death pathways only in the...
Cell death was observed in the early 19th century, but there was no experimental evidence to prove it. In 1842, Carl Vogt first discovered cell death in a metamorphic toad; however, it was not termed ‘cell death.’ Scientists discovered different cell death pathways only in the...
6.3K
01:16Necrosis
3.9K
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...
3.9K
01:24Peroxisomes
9.2K
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...
9.2K
01:18Autophagic Cell Death
3.0K
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...
3.0K