Selective oxidative stress induces dual damage to telomeres and mitochondria in human T cells.
Selective oxidative stress induces dual damage to telomeres and mitochondria in human T cells.
复制标题
DOI：
10.1111/acel.13513
复制
发表时间：
2021-12
期刊：
影响因子：
7.8
通讯作者：
Yao ZQ
中科院分区：
文献类型：
--
作者：
Wang L;Lu Z;Zhao J;Schank M;Cao D;Dang X;Nguyen LN;Nguyen LNT;Khanal S;Zhang J;Wu XY;El Gazzar M;Ning S;Moorman JP;Yao ZQ
由过量活性氧（ROS）引起的氧化应激加速端粒侵蚀和线粒体损伤，导致细胞功能受损和细胞死亡。氧化应激介导的端粒侵蚀是否会诱导人类T细胞中的线粒体损伤，反之亦然，由于ROS的多效性作用，对宿主获得性免疫对抗感染和恶性肿瘤的主要效应子知之甚少。在这里，我们采用了一种新的化学光遗传学工具，该工具选择性地仅在Jurkat T细胞的端粒或线粒体中产生单个氧（1O2）。我们发现，有针对性的1O2在端粒的生产不仅触发端粒DNA损伤，但线粒体功能障碍，导致T细胞凋亡死亡。相反，有针对性的1O2在线粒体的形成不仅诱导线粒体损伤，而且端粒DNA损伤，导致细胞危机和凋亡。靶向端粒或线粒体的氧化应激增加ROS的产生，而在氧化应激过程中阻断ROS的形成逆转了端粒损伤、线粒体功能障碍和细胞凋亡。值得注意的是，碱基切除修复（BER）途径中的X射线修复交叉互补蛋白1（XRCC1）和其他细胞途径中的多种线粒体蛋白质因靶向氧化应激而失调。通过将单线态1O2形成限制在单个细胞器中，这项研究表明，氧化应激通过端粒和线粒体之间的串扰诱导T细胞的双重损伤。进一步鉴定这些氧化途径可能会提供一种新的方法来保护线粒体功能、保护端粒完整性和维持T细胞存活，可用于对抗各种免疫衰老相关疾病。由过量活性氧（ROS）引起的氧化应激加速端粒侵蚀和线粒体损伤，导致细胞功能受损和细胞死亡。通过选择性地产生单线态1O2到单个细胞器，Wang和Lu等人证明氧化应激通过端粒和线粒体之间的串扰诱导T细胞的双重损伤，并探索促进这种双重损伤的潜在分子和途径。
Oxidative stress caused by excess reactive oxygen species (ROS) accelerates telomere erosion and mitochondrial injury, leading to impaired cellular functions and cell death. Whether oxidative stress‐mediated telomere erosion induces mitochondrial injury, or vice versa, in human T cells—the major effectors of host adaptive immunity against infection and malignancy—is poorly understood due to the pleiotropic effects of ROS. Here we employed a novel chemoptogenetic tool that selectively produces a single oxygen (1O2) only at telomeres or mitochondria in Jurkat T cells. We found that targeted 1O2 production at telomeres triggered not only telomeric DNA damage but also mitochondrial dysfunction, resulting in T cell apoptotic death. Conversely, targeted 1O2 formation at mitochondria induced not only mitochondrial injury but also telomeric DNA damage, leading to cellular crisis and apoptosis. Targeted oxidative stress at either telomeres or mitochondria increased ROS production, whereas blocking ROS formation during oxidative stress reversed the telomeric injury, mitochondrial dysfunction, and cellular apoptosis. Notably, the X‐ray repair cross‐complementing protein 1 (XRCC1) in the base excision repair (BER) pathway and multiple mitochondrial proteins in other cellular pathways were dysregulated by the targeted oxidative stress. By confining singlet 1O2 formation to a single organelle, this study suggests that oxidative stress induces dual injury in T cells via crosstalk between telomeres and mitochondria. Further identification of these oxidation pathways may offer a novel approach to preserve mitochondrial functions, protect telomere integrity, and maintain T cell survival, which can be exploited to combat various immune aging‐associated diseases. Oxidative stress caused by excess reactive oxygen species (ROS) accelerates telomere erosion and mitochondrial injury, leading to impaired cellular functions and cell death. By selectively producing singlet 1O2 to a single organelle, Wang and Lu et al. demonstrate that oxidative stress induces dual injury in T cells via crosstalk between telomeres and mitochondria, and also explore potential molecules and pathways that promote this dual‐damage.
登录
查看更多内容
影响因子：
16.8
作者：
Arnoult N;Karlseder J
通讯作者：
Karlseder J
DOI：
10.15252/embj.201592862
发表时间：
2016-04-01
期刊：
The EMBO journal
影响因子：
--
作者：
Correia-Melo C;Marques FD;Anderson R;Hewitt G;Hewitt R;Cole J;Carroll BM;Miwa S;Birch J;Merz A;Rushton MD;Charles M;Jurk D;Tait SW;Czapiewski R;Greaves L;Nelson G;Bohlooly-Y M;Rodriguez-Cuenca S;Vidal-Puig A;Mann D;Saretzki G;Quarato G;Green DR;Adams PD;von Zglinicki T;Korolchuk VI;Passos JF
通讯作者：
Passos JF
影响因子：
2
作者：
Arkus, N
通讯作者：
Arkus, N
影响因子：
4.8
作者：
Henle, ES;Han, ZX;Linn, S
通讯作者：
Linn, S
影响因子：
48
作者：
He J;Wang Y;Missinato MA;Onuoha E;Perkins LA;Watkins SC;St Croix CM;Tsang M;Bruchez MP
通讯作者：
Bruchez MP