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哺乳动物细胞线粒体生物合成与mtDNA的维持紧密相关。哺乳动物细胞包含 2～10个mtDNA拷贝，它们是环形的双链DNA分子 [85] 。mtDNA的复制主要发生在细胞分裂周期的S晚期和G2期，但也可能发生在整个细胞分裂期。而且，mtDNA的复制并不与线粒体的增长和分裂同时发生。因此，mtDNA的复制可能与线粒体的增殖并不偶联，但mtDNA的维持对线粒体生物合成是必要的。哺乳动物细胞mtDNA的维持不仅需要精确的mtDNA复制，而且需要mtDNA的修复和重组。mtDNA的完整性可以影响细胞内mtDNA的维持。人类mtDNA由于其缺乏保护作用的组蛋白，而且DNA修复能力有限，对氧化损伤更为敏感，暴露于呼吸过程中产生的高水平ROS时，相对于核DNA有更高的突变率 [86] 。
为了应对有氧代谢过程中不断产生的ROS，细胞拥有抗氧化酶系，包括线粒体MnSOD、Cu／ZnSOD、GSH-PX和CAT [87] 。大量的其他因子也促进了ROS的防御和抵抗，包括维生素A、维生素C和维生素E以及谷光甘肽。线粒体MnSOD和细胞质的Cu／ZnSOD将超氧阴离子转化为H 2 O 2 ，随后被谷胱甘肽过氧化物酶（GSH-PX）转化为H 2 O或被过氧化氢酶（CAT）转化为H 2 O和O 2 。尽管这些酶系同其他抗氧化剂共同作用可以消除ROS和自由基，但一小部分可以避开抗氧化防御机制引起细胞组分包括核苷酸、蛋白质和脂质等损伤。ROS的过量产生对细胞产生危害，因此任何导致ROS过度产生的信号或刺激都可以引起细胞氧化还原反应危害最终导致细胞死亡。
图1-7 线粒体内抗氧化酶系与ROS的作用机制 ［88］
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