Mitochondrial structure, function and dynamics are temporally controlled by c-Myc.
Mitochondrial structure, function and dynamics are temporally controlled by c-Myc.
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DOI：
10.1371/journal.pone.0037699
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发表时间：
2012
期刊：
影响因子：
3.7
通讯作者：
Prochownik EV
中科院分区：
文献类型：
--
作者：
Graves JA;Wang Y;Sims-Lucas S;Cherok E;Rothermund K;Branca MF;Elster J;Beer-Stolz D;Van Houten B;Vockley J;Prochownik EV
虽然c-Myc（Myc）癌蛋白控制线粒体生物合成和参与氧化磷酸化（OXPHOS）的多种酶，这些事件的协调和其调节的机制基础仍然在很大程度上未被探索。我们在这里表明，Myc在myc−/−成纤维细胞中的重新表达伴随着线粒体生物量的逐渐积累以及膜极化和线粒体融合的增加。还可以看到OXPHOS缺陷的校正，尽管电子传递链复合物（ETC）中的结构异常未完全正常化。相反，Myc的下调导致线粒体质量的逐渐减少以及融合和膜电位的更快损失。特别是参与线粒体分裂和融合的蛋白质水平的增加支持了Myc通过影响这两个过程来影响线粒体质量的想法，尽管有利于后者。Myc恢复后持续存在的ETC缺陷可能代表代谢适应，因为线粒体功能从产生ATP重新定向为提供转化细胞所需的代谢前体来源。
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.
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影响因子：
3.5
作者：
Chen H;Chan DC
通讯作者：
Chan DC
DOI：
10.1083/jcb.200211046
发表时间：
2003-01-20
期刊：
The Journal of cell biology
影响因子：
--
作者：
Chen H;Detmer SA;Ewald AJ;Griffin EE;Fraser SE;Chan DC
通讯作者：
Chan DC
影响因子：
5.2
作者：
Chang CR;Blackstone C
通讯作者：
Blackstone C
DOI：
10.1111/j.1749-6632.2010.05615.x
发表时间：
2010-01-01
期刊：
MITOCHONDRIAL RESEARCH IN TRANSLATIONAL MEDICINE
影响因子：
--
作者：
Chen, Hsiuchen;Chan, David C.
通讯作者：
Chan, David C.
影响因子：
21.3
作者：
Grandori, C;Gomez-Roman, N;White, RJ
通讯作者：
White, RJ