Regulatory crosstalk between the oxidative stress-related transcription factor Nfe212/Nrf2 and mitochondria
Regulatory crosstalk between the oxidative stress-related transcription factor Nfe212/Nrf2 and mitochondria
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DOI：
10.1016/j.taap.2018.09.014
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发表时间：
2018-11-15
影响因子：
3.8
通讯作者：
Kwak, Mi-Kyoung
中科院分区：
文献类型：
--
作者：
Ryoo, In-geun;Kwak, Mi-Kyoung
线粒体在细胞生物能量、生物合成和细胞凋亡中起着重要作用。在呼吸和氧化磷酸化过程中，线粒体利用氧气产生ATP，同时不可避免地产生活性氧（reactive oxygen species， ROS）。由于过量的活性氧产生氧化应激和损伤细胞，抗氧化防御系统的正常功能对真核细胞在有氧条件下的生存至关重要。核因子，红细胞2样2 （Nfe212/Nrf2）是调节基础和诱导多种抗氧化蛋白表达的主转录因子。Nrf2通过提供还原型谷胱甘肽（GSH）参与维持线粒体氧化还原稳态；还原性辅因子NADPH；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和过氧化物还蛋白3/5。此外，最近的研究进展表明，Nrf2通过更多不同的分子间联系参与线粒体调控。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，并通过线粒体自噬激活参与线粒体质量控制系统。此外，多种线粒体蛋白参与调控Nrf2，在线粒体和Nrf2之间形成互惠调控环。此外，Nrf2在癌细胞中的调节导致线粒体呼吸系统和癌症生物能量学的变化，从而全面影响癌症代谢。在这篇综述中，我们描述了Nrf2与线粒体之间关系的最新实验观察，并进一步讨论了Nrf2对癌症线粒体和代谢的影响。
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 (Nfe212/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 mitochondria] 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 mitochondria] 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.