Wolfson Institute for Biomedical Research, University College London, London, UK.
Cell Metab. 2012 Apr 4;15(4):466-79. doi: 10.1016/j.cmet.2012.03.003.
Cell proliferation is associated with a high rate of aerobic glycolysis, which has been widely interpreted as a compensatory mechanism for suppressed mitochondrial function, despite reports of high respiration rates. The molecular mechanisms that link cell proliferation with mitochondrial metabolism, dynamics, and biogenesis remain obscure. Here, we show that proliferation is associated with an increase in both glycolysis and respiration, in conjunction with mitochondrial fusion and biogenesis. Changes in mitochondrial morphology and mass are due to accumulation of OPA1, MFN1, and TFAM, silencing any of which hinders cell proliferation. Moreover, the levels of OPA1, MFN1, and TFAM are regulated by the ubiquitin ligase APC/C(CDH1), which also controls proteasomal degradation of key glycolytic, glutaminolytic, and cell-cycle proteins. Thus, we have identified an important component of the molecular mechanism that coordinates cell proliferation with activation of the mitochondrial metabolic machinery that provides the necessary energy and biosynthetic substrates.
细胞增殖与有氧糖酵解的高速率相关，尽管有报道称呼吸速率很高，但这已被广泛解释为对线粒体功能受抑制的一种代偿机制。将细胞增殖与线粒体代谢、动力学和生物发生联系起来的分子机制仍然不清楚。在这里，我们表明，增殖与糖酵解和呼吸作用的增加有关，伴随着线粒体融合和生物发生。线粒体形态和质量的变化是由于 OPA1、MFN1 和 TFAM 的积累，沉默其中任何一个都会阻碍细胞增殖。此外，OPA1、MFN1 和 TFAM 的水平受泛素连接酶 APC/C（CDH1）的调节，该酶还控制关键糖酵解、谷氨酰胺分解和细胞周期蛋白的蛋白酶体降解。因此，我们已经确定了协调细胞增殖与激活提供必要能量和生物合成底物的线粒体代谢机制的重要组成部分。
