Integrated Research Institute for Pharmaceutical Sciences, The Catholic University of Korea, 43 Jibong-ro, Bucheon 14662, Gyeonggi-do, Republic of Korea.
Integrated Research Institute for Pharmaceutical Sciences, The Catholic University of Korea, 43 Jibong-ro, Bucheon 14662, Gyeonggi-do, Republic of Korea; College of Pharmacy, The Catholic University of Korea, 43 Jibong-ro, Bucheon, Gyeonggi-do 14662, Republic of Korea.
Toxicol Appl Pharmacol. 2018 Nov 15;359:24-33. doi: 10.1016/j.taap.2018.09.014. Epub 2018 Sep 18.
Mitochondria play essential roles in cellular bioenergetics, biosynthesis, and apoptosis. During the process of respiration and oxidative phosphorylation, mitochondria utilize oxygen to generate ATP, and at the same time, there is an inevitable generation of reactive oxygen species (ROS). As excess ROS create oxidative stress and damage cells, the proper function of the antioxidant defense system is critical for eukaryotic cell survival under aerobic conditions. Nuclear factor, erythroid 2-like 2 (Nfe2l2/Nrf2) is a master transcription factor for regulating basal as well as inducible expression of multiple antioxidant proteins. Nrf2 has been involved in maintaining mitochondrial redox homeostasis by providing reduced forms of glutathione (GSH); the reducing cofactor NADPH; and mitochondrial antioxidant enzymes such as GSH peroxidase 1, superoxide dismutase 2, and peroxiredoxin 3/5. In addition, recent research advances suggest that Nrf2 contributes to mitochondrial regulation through more divergent intermolecular linkages. Nrf2 has been positively associated with mitochondrial biogenesis through the direct upregulation of mitochondrial transcription factors and is involved in the mitochondrial quality control system through mitophagy activation. Moreover, several mitochondrial proteins participate in regulating Nrf2 to form a reciprocal regulatory loop between mitochondria and Nrf2. Additionally, Nrf2 modulation in cancer cells leads to changes in the mitochondrial respiration system and cancer bioenergetics that overall affect cancer metabolism. In this review, we describe recent experimental observations on the relationship between Nrf2 and mitochondria, and further discuss the effects of Nrf2 on cancer mitochondria and metabolism.
线粒体在细胞生物能量学、生物合成和细胞凋亡中发挥着重要作用。在呼吸和氧化磷酸化过程中，线粒体利用氧气生成 ATP，同时不可避免地会产生活性氧（ROS）。由于过量的 ROS 会造成氧化应激并损伤细胞，因此抗氧化防御系统的正常功能对于需氧条件下真核细胞的存活至关重要。核因子，红系 2 相关因子 2（Nfe2l2/Nrf2）是调节多种抗氧化蛋白基础和诱导表达的主要转录因子。Nrf2 通过提供还原型谷胱甘肽（GSH）、还原辅酶 NADPH 和线粒体抗氧化酶如谷胱甘肽过氧化物酶 1、超氧化物歧化酶 2 和过氧化物酶 3/5 来参与维持线粒体的氧化还原稳态。此外，最近的研究进展表明，Nrf2 通过更不同的分子间联系为线粒体调节做出贡献。Nrf2 通过直接上调线粒体转录因子与线粒体生物发生呈正相关，并通过激活线粒体自噬参与线粒体质量控制系统。此外，几种线粒体蛋白参与调节 Nrf2，从而在线粒体和 Nrf2 之间形成一个相互调节的循环。此外，癌细胞中 Nrf2 的调节会导致线粒体呼吸系统和癌症生物能量的变化，从而整体影响癌症代谢。在这篇综述中，我们描述了最近关于 Nrf2 与线粒体之间关系的实验观察，并进一步讨论了 Nrf2 对癌症线粒体和代谢的影响。
