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| 1 | Tom20 senses iron-activated ROS signaling to promote melanoma cell pyroptosis显示文摘Iron has been shown to trigger oxidative stress by elevating reactive oxygen species (ROS) and to participate in different modes of cell death,such as ferroptosis,apoptosis and necroptosis. However,whether iron-elevated ROS is also linked to pyroptosis has not been reported. Here,we demonstrate that iron-activated ROS can induce pyroptosis via a Tom20-Bax-caspase-GSDME pathway. In melanoma cells,iron enhanced ROS signaling initiated by CCCP,causing the oxidation and oligomerization of the mitochondrial outer membrane protein Tom20. Bax is recruited to mitochondria by oxidized Tom20,which facilitates cytochrome c release to cytosol to activate caspase-3;eventually triggering pyroptotic death by inducing GSDME cleavage. Therefore,ROS acts as a causative factor and Tom20 senses ROS signaling for iron-driven pyroptotic death of melanoma cells. Since iron activates ROS for GSDME-dependent pyroptosis induction and melanoma cells specifically express a high level of GSDME,iron may be a potential candidate for melanoma therapy. Based on the functional mechanism of iron shown above,we further demonstrate that iron supplementation at a dosage used in iron-deficient patients is sufficient to maximize the anti-tumor effect of clinical ROS-inducing drugs to inhibit xenograft tumor growth and metastasis of melanoma cells through GSDME-dependent pyroptosis. Moreover,no obvious side effects are observed in the normal tissues and organs of mice during the combined treatment of clinical drugs and iron. This study not only identifies iron as a sensitizer amplifying ROS signaling to drive pyroptosis,but also implicates a novel iron-based intervention strategy for melanoma therapy. | Bo Zhou Jia-yuan Zhang Xian-shuo Liu Hang-zi Chen Yuan-li Ai Kang Cheng Ru-yue Sun Dawang Zhou Jiahuai Han Qiao Wu | 2018 | Cell Research2018，28，12： | 52 |
| 2 | Both metaxin and Tom20 together with two mitochondria-specific motifs support mitochondrial targeting of dual-targeting AtSufE1显示文摘Plant cells have two endosymbiotic organelles,chloroplasts,and mitochondria.These organelles perform specific functions that depend on organelle-specific proteins.The majority of chloroplast and mitochondrial proteins are specifically imported by the transit peptide and presequence,respectively.However,a significant number of proteins are also dually targeted to these two organelles.Currently,it is not fully understood how proteins are dually targeted to both chloroplasts and mitochondria.In this study,the mechanism underlying mitochondrial targeting of dual targeting At Suf E1 in Arabidopsis was elucidated.The N-terminal fragment containing 80 residues of AtSufE1(AtSufE1N80)was sufficient to confer dual targeting of reporter protein,At SufE1N80:GFP,in protoplasts.Two sequence motifs,two arginine residues at 15and 21positions,and amino acid(aa)sequence motif AKTLLLRPLK from the 31to 40aa position,were responsible for targeting to mitochondria a portion of reporter proteins amid the chloroplast targeting.The sequence motif PSEVPFRRT from the 41 stto 50 thaa position constitutes a common motif for targeting to both chloroplasts and mitochondria.For mitochondrial import of At Suf E1:N80,Metaxin played a critical role.In addition,Bi FC and protein pull-down experiments showed that At Suf E1N80 specifically interacts with import receptors,Metaxin and Tom20.The interaction of At Suf E1N80 with Metaxin was required for the interaction with Tom20.Based on these results,we propose that mitochondrial targeting of dual-targeting At Suf E1 is mediated by both mitochondria-specific and common sequence motifs in the signal sequence through the interaction with import receptors,Metaxin and Tom20,in a successive manner. | Seungjin Woo Byeongho Moon Inhwan Hwang | 2022 | Journal of Integrative Plant Biology2022，64，8： | 0 |
| 3 | 线粒体膜蛋白Tom20在甲状腺增生病中的表达及意义显示文摘目的阐明线粒体膜蛋白Tom20在甲状腺增生病中的表达和临床意义.方法选择2018年1月—2019年12月在本院行甲状腺疾病手术治疗的40例患者作为研究对象,手术切除甲状腺病理组织以及周围正常甲状腺组织,分为良性增生组(n=3)和甲状腺癌组(n=37)两组,甲状腺正常组织为正常组(n=40).Western blot分析三组甲状腺组织Tom20表达,Realtime PCR和人ELISA分别检测三组Tom20 mRNA表达以及Tom20蛋白含量.结果正常组Tom20相对表达量为(0.93±0.12);良性增生组、甲状腺癌组Tom20相对表达量分别为(0.68±0.10)和(0.33±0.13),差异具有统计学意义(P<0.01);相对于正常组Tom20含量(813.24±2.07)ng/ml,良性增生组、甲状腺癌组Tom20含量分别为(525.97±1.18)ng/ml和(167.30±1.94)ng/ml,差异具有统计学意义(P<0.01);正常组、良性增生组、甲状腺癌组Tom20 mRNA相对表达分别为(0.76±0.08)、(0.41±0.07)和(0.23±0.01),差异具有统计学意义(P<0.01).结论良性甲状腺增生、甲状腺癌中线粒体膜蛋白Tom20呈现低表达. | 车立群 任博 贾媛媛 董羽佳 王艳冰 单洁 | 2020 | 齐齐哈尔医学院学报2020，41，22： | 0 |
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