TRAF3: A novel regulator of mitochondrial physiology and metabolic pathways in B lymphocytes.

TRAF3: A novel regulator of mitochondrial physiology and metabolic pathways in B lymphocytes.
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DOI:
10.3389/fonc.2023.1081253
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发表时间:
2023
影响因子:
4.7
通讯作者:
--
中科院分区:
医学3区
文献类型:
--
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线粒体是细胞生存和新陈代谢的关键细胞器,被癌细胞利用,是癌症治疗的重要靶点。线粒体动态地进行分裂和融合,以保持其不同的功能。控制线粒体分裂和融合的蛋白质被认为是线粒体功能、线粒体质量控制和细胞生存的重要调节因子。在最近的蛋白质组学研究中,我们确定了关键的线粒体裂变因子MFf是TRAF3的一种新的相互作用蛋白,TRAF3是多发性骨髓瘤和其他B细胞恶性肿瘤的已知肿瘤抑制因子。这种相互作用将大多数细胞质中的TRAF3招募到线粒体,使TRAF3能够调节线粒体的形态、功能和静息B淋巴细胞中线粒体依赖的凋亡。有趣的是,最近的转录学、代谢和脂体学研究表明,TRAF3还重要地调节B细胞的多种代谢途径,包括磷脂代谢、葡萄糖代谢和核苷酸代谢。因此,TRAF3被认为是B淋巴细胞和B细胞恶性肿瘤中线粒体生理和代谢途径的一种新的调节因子。在这里,我们回顾目前在这一领域的知识,并讨论相关的临床意义。
Mitochondria, the organelle critical for cell survival and metabolism, are exploited by cancer cells and provide an important therapeutic target in cancers. Mitochondria dynamically undergo fission and fusion to maintain their diverse functions. Proteins controlling mitochondrial fission and fusion have been recognized as essential regulators of mitochondrial functions, mitochondrial quality control, and cell survival. In a recent proteomic study, we identified the key mitochondrial fission factor, MFF, as a new interacting protein of TRAF3, a known tumor suppressor of multiple myeloma and other B cell malignancies. This interaction recruits the majority of cytoplasmic TRAF3 to mitochondria, allowing TRAF3 to regulate mitochondrial morphology, mitochondrial functions, and mitochondria-dependent apoptosis in resting B lymphocytes. Interestingly, recent transcriptomic, metabolic and lipidomic studies have revealed that TRAF3 also vitally regulates multiple metabolic pathways in B cells, including phospholipid metabolism, glucose metabolism, and ribonucleotide metabolism. Thus, TRAF3 emerges as a novel regulator of mitochondrial physiology and metabolic pathways in B lymphocytes and B cell malignancies. Here we review current knowledge in this area and discuss relevant clinical implications.
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