Structural and functional remodeling of mitochondria as an adaptive response to energy deprivation.
Structural and functional remodeling of mitochondria as an adaptive response to energy deprivation.
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DOI：
10.1016/j.bbabio.2021.148393
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发表时间：
2021-06-01
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影响因子：
--
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癌细胞的生物能量学更依赖于糖酵解而不是线粒体氧化磷酸化，这种现象被称为Warburg效应。有人提出糖酵解的抑制可能选择性地影响癌细胞。然而，糖酵解抑制对癌细胞线粒体功能和结构的影响尚不完全清楚。在这里，我们研究了2-脱氧-d-葡萄糖（2-DG，一种抑制细胞糖酵解的葡萄糖类似物）对人结肠癌DLD-1细胞、平滑肌细胞、人脐静脉内皮细胞和HL-1心肌细胞生物能量学的比较影响。在所有细胞中，2-DG处理导致明显的ATP消耗，但细胞活力保持不变。此外，我们没有观察到2-DG与抗癌药物阿霉素和5-氟尿嘧啶的协同作用。相反，经过2-DG处理和ATP消耗后，线粒体呼吸和膜电位显著增强，线粒体形态朝着更多网络组织的方向变化。蛋白表达分析表明，2- dg处理诱导AMPK活化（pAMPK/AMPK比值升高），线粒体融合（mitofusins 1和2）增加，裂变（Drp1）蛋白减少。总之，本研究表明呼吸功能与细胞线粒体结构组织之间存在密切联系。我们认为，与断开的线粒体相比，线粒体网络的功能得到增强。
Cancer cells bioenergetics is more dependent on glycolysis than mitochondrial oxidative phosphorylation, a phenomenon known as the Warburg Effect. It has been proposed that inhibition of glycolysis may selectively affect cancer cells. However, the effects of glycolysis inhibition on mitochondrial function and structure in cancer cells are not completely understood. Here, we investigated the comparative effects of 2-deoxy-d-glucose (2-DG, a glucose analogue, which suppresses cellular glycolysis) on cellular bioenergetics in human colon cancer DLD-1 cells, smooth muscle cells, human umbilical vein endothelial cells and HL-1 cardiomyocytes. In all cells, 2-DG treatment resulted in significant ATP depletion, however, the cell viability remained unchanged. Also, we did not observe the synergistic effects of 2-DG with anticancer drugs doxorubicin and 5-fluorouracil. Instead, after 2-DG treatment and ATP depletion, mitochondrial respiration and membrane potential were significantly enhanced and mitochondrial morphology changed in the direction of more network organization. Analysis of protein expression demonstrated that 2-DG treatment induced an activation of AMPK (elevated pAMPK/AMPK ratio), increased mitochondrial fusion (mitofusins 1 and 2) and decreased fission (Drp1) proteins. In conclusion, this study suggests a strong link between respiratory function and structural organization of mitochondria in the cell. We propose that the functionality of the mitochondrial network is enhanced compared to disconnected mitochondria.
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影响因子：
16.6
作者：
Anderson GR;Wardell SE;Cakir M;Yip C;Ahn YR;Ali M;Yllanes AP;Chao CA;McDonnell DP;Wood KC
通讯作者：
Wood KC
影响因子：
12.8
作者：
Kim J;Yang G;Kim Y;Kim J;Ha J
通讯作者：
Ha J
影响因子：
4.3
作者：
Ertel, Adam;Tsirigos, Aristotelis;Lisanti, Michael P.
通讯作者：
Lisanti, Michael P.
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
Mfn2 消融会导致海马和皮质中的氧化应激反应并最终导致神经元死亡
影响因子：
15.1
作者：
Jiang S;Nandy P;Wang W;Ma X;Hsia J;Wang C;Wang Z;Niu M;Siedlak SL;Torres S;Fujioka H;Xu Y;Lee HG;Perry G;Liu J;Zhu X
通讯作者：
Zhu X