蛋白质合成的偏差调节和因条件猛禽突变导致的低氧死亡
Chun-Ling Sun1, Cong Xu1, Omar Itani1
1Department of Anesthesiology and Pain Medicine, University of Washington, Box 356540, 1959 NE Pacific Street, Seattle, WA 98195, USA; Mitochondrial and Metabolism Center, University of Washington, 850 Republican Street, Seattle, WA 98109, USA.
Current biology : CB
|May 8, 2025
概括
在C. elegans中,一种新型的温度敏感猛禽突变通过减少蛋白质合成来赋予低氧耐药性. 这一发现突显了猛禽-RagA相互作用在调节细胞对缺氧和长寿反应中的关键作用.
科学领域:
- 细胞生物学 细胞生物学
- 遗传学 遗传学 是一个
- 生理学 生理学 生理学
背景情况:
- 拉巴胺素 (mTOR) 途径的机械性标,特别是与猛禽的mTOR复合体1 (mTORC1),调节新陈代谢和细胞过程.
- mTORC1在低氧细胞损伤中的作用尚未完全理解,其保护性或有害作用尚不确定.
研究的目的:
- 研究mTORC1通路在低氧细胞损伤中的作用.
- 确定控制低氧耐药性和寿命的新型机制.
主要方法:
- 在C. elegans中使用了无偏向的前进突变发生屏幕来识别对温度敏感的猛禽突变物.
- 进行了温度转移实验,以评估条件低氧抵抗.
- 进行了表观性实验,以阐明涉及的遗传相互作用和调节机制.
主要成果:
- 发现了一种抗缺氧,对温度敏感的猛禽突变体,在中间温度下表现出延长寿命.
- 证明猛禽突变通过选择性地减少蛋白质合成而不会影响自,从而赋予有条件的缺氧抵抗.
- 在猛禽中发现了抑制突变,可以恢复正常的蛋白质合成和低氧敏感性,涉及猛禽-RagA相互作用.
结论:
- 猛禽-RagA相互作用对于调节蛋白质合成,缺氧敏感性和寿命至关重要.
- 猛禽调节的mTORC1信号传递在细胞适应低氧压力的过程中起着重要作用.
- 针对mTORC1-介导的翻译调节可能为缺氧损伤提供治疗策略.
相关概念视频
Regulation of Expression at Multiple Steps
875
The gene expression in cells is regulated at different stages: (i) transcription, (ii) RNA processing, (iii) RNA localization, and (iv) translation. Transcriptional regulation is mediated by regulatory proteins such as transcription factors, activators, or repressors—these control gene expression by initiating or inhibiting the transcription of genes. Once a precursor or pre-mRNA is produced, it undergoes post-transcriptional modification, including 5' capping, splicing, and the...
875
Regulation of the Unfolded Protein Response
2.4K
Inositol-requiring kinase one or IRE1 is the most conserved eukaryotic unfolded protein response (UPR) receptor. It is a type I transmembrane protein kinase receptor with a distinctive site-specific RNase activity. As the binding mechanics of the misfolded proteins with the N-terminal domain of IRE-1 are unclear, three binding models — direct, indirect, and allosteric -- are proposed for receptor activation. Nevertheless, it is known that once a misfolded protein associates with IRE1, it...
2.4K
PI3K/mTOR/AKT Signaling Pathway
3.4K
The mammalian target of rapamycin (mTOR) is a serine/threonine kinase that regulates growth, proliferation, and cell survival in response to hormones, growth factors, or nutrient availability. This kinase exists in two structurally and functionally distinct forms: mTOR complex 1 (mTORC1) and mTOR complex 2 (mTORC2). The first form (mTORC1) is composed of a rapamycin-sensitive Raptor and proline-rich Akt substrate, PRAS40. In contrast, mTORC2 consists of a...
3.4K
Regulation of Expression Occurs at Multiple Steps
22.5K
Gene expression can be regulated at almost every step from gene to protein. Transcription is the step that is most commonly regulated. This involves the binding of proteins to short regulatory sequences on the DNA. This association can either promote or inhibit the transcription of a gene associated with the respective sequence.
Transcription results in the generation of precursor (pre-mRNA) that consists of both exons and introns, which needs further processing before being translated to a...
Transcription results in the generation of precursor (pre-mRNA) that consists of both exons and introns, which needs further processing before being translated to a...
22.5K
mTOR Signaling and Cancer Progression
3.8K
The mammalian target of rapamycin or mTOR protein was discovered in 1994 due to its direct interaction with rapamycin. The protein gets its name from a yeast homolog called TOR. The mTOR protein complex in mammalian cells plays a major role in balancing anabolic processes such as the synthesis of proteins, lipids, and nucleotides and catabolic processes, such as autophagy in response to environmental cues, such as availability of nutrients and growth factors.
The mTOR pathway or the...
The mTOR pathway or the...
3.8K
Riboswitches
8.1K
Riboswitches are non-coding mRNA domains that regulate the transcription and translation of downstream genes without the help of proteins. Riboswitches bind directly to a metabolite and can form unique stem-loop or hairpin structures in response to the amount of the metabolite present. They have two distinct regions – a metabolite-binding aptamer and an expression platform.
The aptamer has high specificity for a particular metabolite which allows riboswitches to specifically regulate...
The aptamer has high specificity for a particular metabolite which allows riboswitches to specifically regulate...
8.1K


