Redox homeostasis protects mitochondria through accelerating ROS conversion to enhance hypoxia resistance in cancer cells.
Redox homeostasis protects mitochondria through accelerating ROS conversion to enhance hypoxia resistance in cancer cells.
复制标题
氧化还原稳态通过加速 ROS 转化来保护线粒体，从而增强癌细胞的耐缺氧能力。
DOI：
10.1038/srep22831
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发表时间：
2016-03-09
影响因子：
4.6
通讯作者：
Shi D
中科院分区：
文献类型：
--
作者：
Li P;Zhang D;Shen L;Dong K;Wu M;Ou Z;Shi D
线粒体是真核细胞的发电站，是缺氧细胞中活性氧的主要来源，参与调节氧化还原稳态。肿瘤耐缺氧的机制，特别是线粒体在肿瘤耐缺氧中的作用尚不清楚。本研究旨在探讨线粒体在肿瘤耐缺氧中的作用。我们观察到缺氧癌细胞中的糖酵解上调得更快，有氧氧化的衰减要小得多，因此有助于更稳定的ATP/ADP比率。在缺氧时，癌细胞迅速将缺氧诱导的O2·−转化为H2 O2。H2 O2被相对较强的抗氧化系统进一步分解，导致ROS水平与正常细胞相比增加较少。适度的ROS导致适当程度的自噬，消除受损的线粒体，并提供营养以促进线粒体融合，从而保护线粒体并提高癌症的耐缺氧性。功能性线粒体可以使肿瘤细胞在糖酵解和氧化磷酸化之间灵活切换，以满足肿瘤生长的缺氧/复氧循环过程中的不同生理需求。
Mitochondria are the powerhouses of eukaryotic cells and the main source of reactive oxygen species (ROS) in hypoxic cells, participating in regulating redox homeostasis. The mechanism of tumor hypoxia tolerance, especially the role of mitochondria in tumor hypoxia resistance remains largely unknown. This study aimed to explore the role of mitochondria in tumor hypoxia resistance. We observed that glycolysis in hypoxic cancer cells was up-regulated more rapidly, with far lesser attenuation in aerobic oxidation, thus contributing to a more stable ATP/ADP ratio. In hypoxia, cancer cells rapidly convert hypoxia-induced O2·− into H2O2. H2O2 is further decomposed by a relatively stronger antioxidant system, causing ROS levels to increase lesser compared to normal cells. The moderate ROS leads to an appropriate degree of autophagy, eliminating the damaged mitochondria and offering nutrients to promote mitochondria fusion, thus protects mitochondria and improves hypoxia tolerance in cancer. The functional mitochondria could enable tumor cells to flexibly switch between glycolysis and oxidative phosphorylation to meet the different physiological requirements during the hypoxia/re-oxygenation cycling of tumor growth.