Mitochondria play a central role in regulating cellular energy metabolism. However, the present understanding of mitochondria has changed from its unipotent functions to pluripotent and insists on understanding the role of mitochondria not only in regulating the life and death of cells, but in pathological conditions such as cancer. Unlike other cellular organelles, subtle alterations in mitochondrial organization may significantly influence the balance between metabolic networks and cellular behavior. Therefore, the delicate balance between the fusion and fission dynamics of mitochondrion can indicate cell fate. Here, we present mitochondrial chaperone TRAP1 influence on mitochondrial architecture and its correlation with tumor growth and metastasis. We show that TRAP1 overexpression (TRAP1 OE) promotes mitochondrial fission, whereas, TRAP1 knockdown (TRAP1 KD) promotes mitochondrial fusion. Interestingly, TRAP1 OE or KD had a negligible effect on mitochondrial integrity. However, TRAP1 OE cells exhibited enhanced proliferative potential, while TRAP1 KD cells showing increased doubling time. Further, TRAP1 dependent mitochondrial dynamic alterations appeared to be unique since mitochondrial localization of TRAP1 is a mandate for dynamic changes. The expression patterns of fusion and fission genes have failed to correlate with TRAP1 expression, indicating a possibility that the dynamic changes can be independent of these genes. In agreement with enhanced proliferative potential, TRAP1 OE cells also exhibited enhanced migration in vitro and tumor metastasis in vivo. Further, TRAP1 OE cells showed altered homing properties, which may challenge site-specific anticancer treatments. Our findings unravel the TRAP1 role in tumor metastasis, which is in addition to altered energy metabolism.

中文翻译：

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线粒体伴侣蛋白，TRAP1 调节线粒体动力学并促进肿瘤转移

线粒体在调节细胞能量代谢中起着核心作用。然而，目前对线粒体的认识已经从其单能功能转变为多能功能，并坚持理解线粒体不仅在调节细胞生死中的作用，而且在癌症等病理状态中也有作用。与其他细胞器不同，线粒体组织的细微变化可能会显着影响代谢网络和细胞行为之间的平衡。因此，线粒体融合和裂变动力学之间的微妙平衡可以指示细胞命运。在这里，我们介绍了线粒体伴侣 TRAP1 对线粒体结构的影响及其与肿瘤生长和转移的相关性。我们表明 TRAP1 过表达（TRAP1 OE）促进线粒体裂变，而，TRAP1 敲低 (TRAP1 KD) 促进线粒体融合。有趣的是，TRAP1 OE 或 KD 对线粒体完整性的影响可以忽略不计。然而，TRAP1 OE 细胞显示出增强的增殖潜力，而 TRAP1 KD 细胞显示出增加的倍增时间。此外，TRAP1 依赖性线粒体动态改变似乎是独一无二的，因为 TRAP1 的线粒体定位是动态变化的要求。融合和裂变基因的表达模式未能与 TRAP1 表达相关，表明动态变化可能独立于这些基因。与增强的增殖潜力一致，TRAP1 OE 细胞还表现出增强的体外迁移和体内肿瘤转移。此外，TRAP1 OE 细胞显示出改变的归巢特性，这可能会挑战特定部位的抗癌治疗。