Hypoxic Adaptation of Mitochondria and its Impact on Tumor Cell Function.
Hypoxic Adaptation of Mitochondria and its Impact on Tumor Cell Function.
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DOI：
10.1016/j.semcancer.2024.03.004
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发表时间：
2024-03
影响因子：
14.5
通讯作者：
M. Benej;I. Papandreou;N. Denko
中科院分区：
文献类型：
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作者：
M. Benej;I. Papandreou;N. Denko
线粒体是细胞中氧气的主要储存库，在ATP生产过程中消耗氧气。因此，当肿瘤中的环境氧水平下降时，需要进行显著的适应。线粒体活性也是生物合成前体的主要生产者和细胞氧化和还原平衡的调节器。由于复杂的生物化学，线粒体对缺氧的适应是通过多种机制发生的，并对其他细胞过程如大分子合成和基因调控有重要影响。肿瘤缺氧时，线粒体在细胞中的位置发生改变，加速了细胞的裂变和质量控制途径。缺氧线粒体的碳代谢和电子传递等基本代谢途径也发生了显著变化。这些代谢变化进一步影响核表观基因组，因为线粒体代谢物被用作修饰染色质的酶底物。这种协调反应在低氧环境应激下提供生理灵活性和增加肿瘤细胞的稳健性。
Mitochondria are the major sink for oxygen in the cell, consuming it during ATP production. Therefore, when environmental oxygen levels drop in the tumor, significant adaptation is required. Mitochondrial activity is also a major producer of biosynthetic precursors and a regulator of cellular oxidative and reductive balance. Because of the complex biochemistry, mitochondrial adaptation to hypoxia occurs through multiple mechanisms and has significant impact on other cellular processes such as macromolecule synthesis and gene regulation. In tumor hypoxia, mitochondria shift their location in the cell and accelerate the fission and quality control pathways. Hypoxic mitochondria also undergo significant changes to fundamental metabolic pathways of carbon metabolism and electron transport. These metabolic changes further impact the nuclear epigenome because mitochondrial metabolites are used as enzymatic substrates for modifying chromatin. This coordinated response delivers physiological flexibility and increased tumor cell robustness during the environmental stress of low oxygen.