Glucose-modulated mitochondria adaptation in tumor cells: a focus on ATP synthase and inhibitor Factor 1.
Glucose-modulated mitochondria adaptation in tumor cells: a focus on ATP synthase and inhibitor Factor 1.
复制标题
DOI：
10.3390/ijms13021933
复制
发表时间：
2012
影响因子：
5.6
通讯作者：
Mavelli I
中科院分区：
文献类型：
--
作者：
Domenis R;Bisetto E;Rossi D;Comelli M;Mavelli I
Warburg的假设受到了一些研究的挑战，这些研究表明氧化磷酸化在某些肿瘤中受到抑制，而不是本身不活跃。因此，能够通过激活线粒体途径来改变能量代谢的治疗被认为是优化抗肿瘤策略的一个有趣的基础。在这项研究中，HepG2肝癌细胞在模拟“阳性”（激活/生物发生）或“阴性”（沉默）线粒体适应的条件下，用不同的代谢底物培养。除了预期的线粒体生物发生上调外，葡萄糖剥夺还导致磷酸化呼吸增加，ATP合成酶β亚基和抑制因子1 （IF1）的表达水平升高。另一方面，高血糖导致转录辅激活因子PGC-α水平显著降低，表明线粒体生物发生下调，但线粒体质量未发生变化，磷酸化呼吸未受到损害。此外，线粒体网络和ATP合酶二聚体稳定性降低。对β-ATP合成酶表达无影响。值得注意的是，高血糖引起IF1表达水平升高，但没有改变与ATP合酶相关的IF1的量。这些结果表明，IF1除了对线粒体ATP合酶调节的众所周知的作用外，还与肿瘤细胞的高糖利用有关。
Warburg’s hypothesis has been challenged by a number of studies showing that oxidative phosphorylation is repressed in some tumors, rather than being inactive per se. Thus, treatments able to shift energy metabolism by activating mitochondrial pathways have been suggested as an intriguing basis for the optimization of antitumor strategies. In this study, HepG2 hepatocarcinoma cells were cultivated with different metabolic substrates under conditions mimicking “positive” (activation/biogenesis) or “negative” (silencing) mitochondrial adaptation. In addition to the expected up-regulation of mitochondrial biogenesis, glucose deprivation caused an increase in phosphorylating respiration and a rise in the expression levels of the ATP synthase β subunit and Inhibitor Factor 1 (IF1). Hyperglycemia, on the other hand, led to a markedly decreased level of the transcriptional coactivator PGC-α suggesting down-regulation of mitochondrial biogenesis, although no change in mitochondrial mass and no impairment of phosphorylating respiration were observed. Moreover, a reduction in mitochondrial networking and in ATP synthase dimer stability was produced. No effect on β-ATP synthase expression was elicited. Notably, hyperglycemia caused an increase in IF1 expression levels, but it did not alter the amount of IF1 associated with ATP synthase. These results point to a new role of IF1 in relation to high glucose utilization by tumor cells, in addition to its well known effect upon mitochondrial ATP synthase regulation.
登录
查看更多内容
DOI：
10.1016/s0006-291x(88)80429-7
发表时间：
1988-05-16
影响因子：
3.1
作者：
DIPIETRO, A;PENIN, F;GAUTHERON, DC
通讯作者：
GAUTHERON, DC
影响因子：
4.8
作者：
Rouslin, W;Broge, CW
通讯作者：
Broge, CW
影响因子：
3
作者：
Smolkova, Katarina;Bellance, Nadege;Rossignol, Rodrigue
通讯作者：
Rossignol, Rodrigue
影响因子：
3.9
作者：
CHERNYAK, BV;DUKHOVICH, VF;KHODJAEV, EY
通讯作者：
KHODJAEV, EY
影响因子：
11.4
作者：
Paumard, P;Vaillier, J;Velours, J
通讯作者：
Velours, J