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考察氧化应激下 TERT 向线粒体的转移。

Examining transfer of TERT to mitochondria under oxidative stress.

机构信息

Moscow Institute of Physics and Technology (MIPT), 9 Institutsky lane, Dolgoprudny, 141700, Russian Federation.

G.K. Skryabin Institute of Biochemistry and Physiology of Microorganisms, Federal Research Center "Pushchino Scientific Center for Biological Research of the Russian Academy of Sciences", 5 Prospekt Nauki, Pushchino, 142290, Russian Federation.

出版信息

Sci Rep. 2024 Oct 15;14(1):24185. doi: 10.1038/s41598-024-75127-4.

DOI:10.1038/s41598-024-75127-4
PMID:39406807
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11480324/
Abstract

The primary role of telomerase is the lengthening of telomeres. Nonetheless, emerging evidence highlights additional functions of telomerase outside of the nucleus. Specifically, its catalytic subunit, TERT (Telomerase Reverse Transcriptase), is detected in the cytosol and mitochondria. Several studies have suggested an elevation in TERT concentration within mitochondria in response to oxidative stress. However, the origin of this mitochondrial TERT, whether transported from the nucleus or synthesized de novo, remains uncertain. In this study, we investigate the redistribution of TERT, labeled with a SNAP-tag, in response to oxidative stress using laser scanning fluorescence microscopy. Our findings reveal that, under our experimental conditions, there is no discernible transport of TERT from the nucleus to the mitochondria due to oxidative stress.

摘要

端粒酶的主要作用是延长端粒。然而,新出现的证据强调了端粒酶在核外的其他功能。具体来说,它的催化亚基,TERT(端粒酶逆转录酶),在细胞质和线粒体中被检测到。几项研究表明,在氧化应激的情况下,线粒体中端粒酶的浓度升高。然而,这种线粒体 TERT 的来源,是从核内运输而来还是从头合成,仍不确定。在这项研究中,我们使用激光扫描荧光显微镜研究了在氧化应激下,用 SNAP 标签标记的 TERT 的重新分布。我们的发现表明,在我们的实验条件下,由于氧化应激,端粒酶不会从核内明显转运到线粒体。

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1
Examining transfer of TERT to mitochondria under oxidative stress.考察氧化应激下 TERT 向线粒体的转移。
Sci Rep. 2024 Oct 15;14(1):24185. doi: 10.1038/s41598-024-75127-4.
2
Telomerase does not counteract telomere shortening but protects mitochondrial function under oxidative stress.端粒酶并不抵消端粒缩短,而是在氧化应激下保护线粒体功能。
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Downregulation of mitochondrial telomerase reverse transcriptase induced by H2O2 is Src kinase dependent.H2O2 诱导的线粒体端粒酶逆转录酶下调依赖于Src 激酶。
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Mitochondrial telomerase reverse transcriptase binds to and protects mitochondrial DNA and function from damage.线粒体端粒酶逆转录酶与线粒体DNA结合并保护其及线粒体功能免受损伤。
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Hydrogen peroxide triggers nuclear export of telomerase reverse transcriptase via Src kinase family-dependent phosphorylation of tyrosine 707.过氧化氢通过Src激酶家族依赖的酪氨酸707磷酸化触发端粒酶逆转录酶的核输出。
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TERT Extra-Telomeric Roles: Antioxidant Activity and Mitochondrial Protection.TERT 端粒外作用:抗氧化活性和线粒体保护。
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Cellular functions of the dual-targeted catalytic subunit of telomerase, telomerase reverse transcriptase--potential role in senescence and aging.端粒酶双靶向催化亚基端粒酶逆转录酶的细胞功能——在衰老和老化中的潜在作用
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本文引用的文献

1
TERT Extra-Telomeric Roles: Antioxidant Activity and Mitochondrial Protection.TERT 端粒外作用:抗氧化活性和线粒体保护。
Int J Mol Sci. 2023 Feb 23;24(5):4450. doi: 10.3390/ijms24054450.
2
Many Functions of Telomerase Components: Certainties, Doubts, and Inconsistencies.端粒酶成分的多种功能:确定的、有疑问的和不一致的。
Int J Mol Sci. 2022 Dec 2;23(23):15189. doi: 10.3390/ijms232315189.
3
Accessing Mitochondrial Protein Import in Living Cells by Protein Microinjection.通过蛋白质显微注射法研究活细胞中的线粒体蛋白导入
Front Cell Dev Biol. 2021 Jul 7;9:698658. doi: 10.3389/fcell.2021.698658. eCollection 2021.
4
Use of HO to Cause Oxidative Stress, the Catalase Issue.使用 HO 引起氧化应激,涉及过氧化氢酶的问题。
Int J Mol Sci. 2020 Nov 30;21(23):9149. doi: 10.3390/ijms21239149.
5
Mitochondria, Telomeres and Telomerase Subunits.线粒体、端粒与端粒酶亚基
Front Cell Dev Biol. 2019 Nov 6;7:274. doi: 10.3389/fcell.2019.00274. eCollection 2019.
6
Determination of cell nucleus-to-cytoplasmic ratio using imaging flow cytometry and a combined ultrasound and photoacoustic technique: a comparison study.利用成像流式细胞术和联合超声和光声技术测定细胞核-细胞质比率:一项对比研究。
J Biomed Opt. 2019 Oct;24(10):1-10. doi: 10.1117/1.JBO.24.10.106502.
7
TERC promotes cellular inflammatory response independent of telomerase.TERC 促进细胞炎症反应,而不依赖端粒酶。
Nucleic Acids Res. 2019 Sep 5;47(15):8084-8095. doi: 10.1093/nar/gkz584.
8
Expression of functional alternative telomerase RNA component gene in mouse brain and in motor neurons cells protects from oxidative stress.功能性替代端粒酶RNA组分基因在小鼠大脑和运动神经元细胞中的表达可抵御氧化应激。
Oncotarget. 2016 Nov 29;7(48):78297-78309. doi: 10.18632/oncotarget.13049.
9
An antiapoptotic role for telomerase RNA in human immune cells independent of telomere integrity or telomerase enzymatic activity.端粒酶RNA在人类免疫细胞中的抗凋亡作用,与端粒完整性或端粒酶酶活性无关。
Blood. 2014 Dec 11;124(25):3675-84. doi: 10.1182/blood-2014-06-582254. Epub 2014 Oct 15.
10
Site-specific protein labeling with SNAP-tags.使用SNAP标签进行位点特异性蛋白质标记。
Curr Protoc Protein Sci. 2013 Sep 24;73:30.1.1-30.1.16. doi: 10.1002/0471140864.ps3001s73.