近日,来自美国匹兹堡大学医学中心的研究人员发现,c-Myc能够短暂的控制线粒体的结构、功能及动力学变化,相关研究成果于5月21日在线发表在PLoS ONE上。
c-myc基因是myc基因家族的重要成员之一,它既是一种可易位基因,又是一种可调节基因,也是一种能够使细胞无限增殖,获得永生化功能,并促进细胞分裂的基因。c-myc基因与多种肿瘤发生发展有关,其表达产物在调节细胞生长、分化或恶性转化中发挥重要作用。
之前的研究就已经发现,c-Myc (Myc)癌蛋白能够控制粒线体的生物合成以及多种与氧化磷酸化(OXPHOS)有关的酶的功能,但是,这些事件的潜在调节机制目前还不明确。
J. Anthony Graves等人发现,在myc-/-纤维母细胞重表达Myc以后,线粒体的数量会表现出逐渐累积的现象,而且,膜极化以及线粒体融合也出现增加。OXPHOS缺陷也被发现表现出一定程度的修复,虽然电子传递链复合体(ETC)里的结构性异常还没有被标准化。
与之相反,研究人员发现,下调Myc后会导致线粒体质量(mass)逐渐下降,线粒体融合很快减少,而且膜电位也很快损失。
总的来说,与线粒体的分裂及融合特异相关的蛋白的水平增加表明,Myc通过影响这些过程,影响了线粒体的质量。(生物谷Deepblue编译)
doi: 10.1371/journal.pone.0037699
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Mitochondrial Structure, Function and Dynamics Are Temporally Controlled by c-Myc
J. Anthony Graves*, Yudong Wang, Sunder Sims-Lucas, Edward Cherok, Kristi Rothermund, Maria F. Branca, Jennifer Elster, Donna Beer-Stolz, Bennett Van Houten, Jerry Vockley, Edward V. Prochownik.
Although the c-Myc (Myc) oncoprotein controls mitochondrial biogenesis and multiple enzymes involved in oxidative phosphorylation (OXPHOS), the coordination of these events and the mechanistic underpinnings of their regulation remain largely unexplored.We show here that re-expression of Myc in myc-/- fibroblasts is accompanied by a gradual accumulation of mitochondrial biomass and by increases in membrane polarization and mitochondrial fusion.A correction of OXPHOS deficiency is also seen, although structural abnormalities in electron transport chain complexes (ETC) are not entirely normalized.Conversely, the down-regulation of Myc leads to a gradual decrease in mitochondrial mass and a more rapid loss of fusion and membrane potential. Increases in the levels of proteins specifically involved in mitochondrial fission and fusion support the idea that Myc affects mitochondrial mass by influencing both of these processes, albeit favoring the latter.The ETC defects that persist following Myc restoration may represent metabolic adaptations, as mitochondrial function is re-directed away from producing ATP to providing a source of metabolic precursors demanded by the transformed cell.