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A Continuous Add-On Probe Reveals the Nonlinear Enlargement of Mitochondria in Light-Activated Oncosis
Advanced Science ( IF 14.3 ) Pub Date : 2021-07-01 , DOI: 10.1002/advs.202004566
Kang-Nan Wang 1 , Xintian Shao 2, 3, 4 , Zhiqi Tian 5 , Liu-Yi Liu 1 , Chengying Zhang 2, 4, 6 , Cai-Ping Tan 1 , Jie Zhang 7 , Peixue Ling 4, 6 , Fei Liu 4, 6 , Qixin Chen 2, 3, 4 , Jiajie Diao 3 , Zong-Wan Mao 1
Affiliation  

Oncosis, depending on DNA damage and mitochondrial swelling, is an important approach for treating cancer and other diseases. However, little is known about the behavior of mitochondria during oncosis, due to the lack of probes for in situ visual illumination of the mitochondrial membrane and mtDNA. Herein, a mitochondrial lipid and mtDNA dual-labeled probe, MitoMN, and a continuous add-on assay, are designed to image the dynamic process of mitochondria in conditions that are unobservable with current mitochondrial probes. Meanwhile, the MitoMN can induce oncosis in a light-activated manner, which results in the enlargement of mitochondria and the death of cancer cells. Using structured illumination microscopy (SIM), MitoMN-stained mitochondria with a dual-color response reveals, for the first time, how swelled mitochondria interacts and fuses with each other for a nonlinear enlargement to accelerate oncosis into an irreversible stage. With this sign of irreversible oncosis revealed by MitoMN, oncosis can be segregated into three stages, including before oncosis, initial oncosis, and accelerated oncosis.

中文翻译:

一个连续的附加探针揭示了光激活肿瘤中线粒体的非线性扩大

取决于 DNA 损伤和线粒体肿胀的肿瘤病是治疗癌症和其他疾病的重要方法。然而,由于缺乏用于线粒体膜和 mtDNA 原位视觉照明的探针,人们对线粒体在肿瘤形成期间的行为知之甚少。在此,线粒体脂质和 mtDNA 双标记探针MitoMN和连续附加分析旨在对当前线粒体探针无法观察到的条件下的线粒体动态过程进行成像。同时,MitoMN可以以光激活的方式诱导肿瘤发生,从而导致线粒体增大和癌细胞死亡。使用结构照明显微镜 (SIM),MitoMN具有双色反应的染色线粒体首次揭示了膨胀的线粒体如何相互作用并相互融合以实现非线性扩大,从而加速肿瘤进入不可逆阶段。有了MitoMN揭示的这种不可逆肿瘤的迹象,肿瘤可分为三个阶段,包括肿瘤前、初始肿瘤和加速肿瘤。
更新日期:2021-09-09
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