文章：

线粒体Fus1/Tusc2和细胞Ca2+稳态：肿瘤抑制，抗炎和抗衰老的意义

Mitochondrial Fus1/Tusc2 and cellular Ca2+ homeostasis: tumor suppressor, anti-inflammatory and anti-aging implications 

原文发布日期：2022-02-18 

英文摘要：

FUS1/TUSC2 (FUSion1/TUmor Suppressor Candidate 2) is a tumor suppressor gene (TSG) originally described as a member of the TSG cluster from human 3p21.3 chromosomal region frequently deleted in lung cancer. Its role as a TSG in lung, breast, bone, and other cancers was demonstrated by several groups, but molecular mechanisms of its activities are starting to unveil lately. They suggest that Fus1-dependent mechanisms are relevant in etiologies of diseases beyond cancer, such as chronic inflammation, bacterial and viral infections, premature aging, and geriatric diseases. Here, we revisit the discovery of FUS1 gene in the context of tumor initiation and progression, and review 20 years of research into FUS1 functions and its molecular, structural, and biological aspects that have led to its use in clinical trials and gene therapy. We present a data-driven view on how interactions of Fus1 with the mitochondrial Ca2+ (mitoCa2+) transport machinery maintain cellular Ca2+ homeostasis and control cell apoptosis and senescence. This Fus1-mediated cellular homeostasis is at the crux of tumor suppressor, anti-inflammatory and anti-aging activities. 

摘要翻译： 

FUS1/TUSC2（FUSion1/肿瘤抑制候选基因2）是一种肿瘤抑制基因（TSG），最初被描述为人3p21.3染色体区域TSG簇的成员，该区域在肺癌中常发生缺失。多个研究团队已证实其在肺、乳腺、骨骼及其他癌症中的肿瘤抑制功能，但其分子作用机制近期才逐渐揭示。研究表明，Fus1依赖的机制不仅与癌症病因相关，还涉及慢性炎症、细菌与病毒感染、早衰及老年疾病等病理过程。本文回顾了FUS1基因在肿瘤发生与发展背景下的发现过程，系统梳理了二十年来对其功能、分子特性、结构特征及生物学意义的研究进展，这些研究最终推动其进入临床试验与基因治疗应用。我们基于数据驱动视角，解析Fus1如何通过调控线粒体钙离子（mitoCa2+）转运机制维持细胞钙稳态，进而调控细胞凋亡与衰老。这种由Fus1介导的细胞稳态机制，正是其实现肿瘤抑制、抗炎与抗衰老功能的核心所在。

原文链接：

Mitochondrial Fus1/Tusc2 and cellular Ca2+ homeostasis: tumor suppressor, anti-inflammatory and anti-aging implications