Mazure N M, Brahimi-Horn M C, Pouysségur J
University of Nice, CNRS, UMR 6543, Institute of Developmental Biology and Cancer Research, Centre Antoine-Lacassagne, 33, avenue de Valombrose, 06189 Nice, France.
Bull Cancer. 2011 May;98(5):40-6. doi: 10.1684/bdc.2011.1360.
Mitochondria originated from a distant ancestor: the α-proteobacteria. They evolved over millions of years in a symbiotic relationship in eukaryotic cells by favoring consumption of oxygen by the electron transport chain with production of ATP. Contemporary mitochondria still play a crucial role in providing energy but also in apoptosis. Because of this symbiotic relationship and their pivotal function, mitochondria undoubtedly participate in tumorigenesis. Genetic defects in mitochondrial DNA, blockade of oxidative phosphorylation and mitophagy in tumor cells modify the production of damaging reactive oxygen species and restrain apoptosis. As the environment of tumor cells becomes more and more hypoxic, the hypoxia-inducible factor (HIF) is stabilized and participates in the reprogramming of cell metabolism. Recently, we became interested in asking whether HIF and hypoxia affect mitochondrial function. In this review, we show that hypoxia induces enlargement of mitochondria, due to abnormal fusion, which results in resistance to apoptosis and thus in survival. The role of hypoxia-induced BNIP3 and BNIP3L, proteins recently described as pro-survival proteins, in survival is also discussed.
α-变形菌。它们在真核细胞中通过电子传递链消耗氧气并产生ATP的共生关系中进化了数百万年。当代线粒体在提供能量方面仍然起着关键作用，在细胞凋亡中也同样如此。由于这种共生关系及其关键功能，线粒体无疑参与了肿瘤发生。线粒体DNA的遗传缺陷、肿瘤细胞中氧化磷酸化的阻断和线粒体自噬改变了具有损伤性的活性氧的产生并抑制细胞凋亡。随着肿瘤细胞的环境变得越来越缺氧，缺氧诱导因子（HIF）被稳定下来并参与细胞代谢的重编程。最近，我们开始关注HIF和缺氧是否会影响线粒体功能。在这篇综述中，我们表明缺氧会由于异常融合导致线粒体增大，从而产生对细胞凋亡的抗性并因此促进细胞存活。我们还讨论了缺氧诱导的BNIP3和BNIP3L（最近被描述为促存活蛋白）在细胞存活中的作用。
