Bcl-2 induces pro-oxidant state by engaging mitochondrial respiration in tumor cells
Bcl-2 induces pro-oxidant state by engaging mitochondrial respiration in tumor cells
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DOI：
10.1038/sj.cdd.4402165
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发表时间：
2007-09-01
影响因子：
12.4
通讯作者：
Pervaiz, S.
中科院分区：
文献类型：
--
作者：
Chen, Z. X.;Pervaiz, S.
线粒体呼吸是细胞能量产生的关键过程，对细胞增殖、生长和存活至关重要。然而，肿瘤细胞中线粒体呼吸功能的调节还不清楚。在这项研究中，我们提出了一个模型，肿瘤细胞具有微调能量需求和线粒体活性氧（ROS）状态之间的平衡的能力，以维持最佳的生存环境。这是通过调节线粒体呼吸来实现的，取决于细胞器内的ROS环境，主要参与者是Bcl-2和细胞色素c氧化酶（考克斯）。我们报告了一个更高水平的考克斯活性，氧消耗和线粒体呼吸过表达Bcl-2的肿瘤细胞。Bcl-2的瞬时过表达、基因沉默和药理学抑制证实了这些发现。有趣的是，Bcl-2也能够调节线粒体呼吸和考克斯活性，在面对不断增加的ROS水平时，由线粒体复合物抑制剂触发。在这方面，这是合理的建议，Bcl-2可能能够创造一个环境，最适合生存的线粒体呼吸相应地调整，以满足能量需求，而不会引起压倒性的，有害的增加细胞内的活性氧。
Mitochondrial respiration, the key process behind cellular energy production, is critical for cell proliferation, growth and survival. However, the regulation of mitochondrial respiratory function in tumor cells is not well understood. In this study, we propose a model whereby tumor cells possess the capacity to fine-tune the balance between energy demands and mitochondrial reactive oxygen species (ROS) status, to maintain a milieu optimal for survival. This is achieved through the moderation of mitochondrial respiration, depending on the ROS context within the organelle, with the main players being Bcl-2 and cytochrome c oxidase ( COX). We report a higher level of COX activity, oxygen consumption and mitochondrial respiration in tumor cells overexpressing Bcl-2. Transient overexpression, gene silencing and pharmacological inhibition of Bcl-2 corroborate these findings. Interestingly, Bcl-2 is also able to regulate mitochondrial respiration and COX activity in the face of mounting ROS levels, triggered by mitochondrial complex inhibitors. In this respect, it is plausible to suggest that Bcl-2 may be able to create an environment, most suited for survival by adjusting mitochondrial respiration accordingly to meet energy requirements, without incurring an overwhelming, detrimental increase in intracellular ROS.