Singh Jogender
Department of Biological Sciences, Indian Institute of Science Education and Research, Mohali, India.
FEBS J. 2025 Feb 11. doi: 10.1111/febs.70013.
Redox homeostasis, the delicate balance between oxidative and reductive processes, is crucial for cellular function and overall organismal health. At the molecular level, cells need to maintain a fine balance between the levels of reactive oxygen species (ROS) and reducing equivalents such as glutathione and nicotinamide adenine dinucleotide phosphate. The perturbation of redox homeostasis due to excessive ROS production leads to oxidative stress that can damage lipids, proteins, and nucleic acids. Conversely, an overly reduced cellular environment due to overabundant reducing equivalents results in reductive stress, which also interferes with important cellular signaling and physiological processes. Disrupted redox homeostasis is linked to various pathological conditions, including neurodegenerative diseases, inflammatory diseases, cancer, and cardiovascular diseases. Cells employ diverse mechanisms to manage redox imbalance. The hypoxia response pathway, mediated by hypoxia-inducible factors and responsible for sensing and defending against low oxygen levels, plays a vital role in maintaining redox homeostasis. In this review, we highlight the complex and multifaceted crosstalk between hypoxia-inducible factors and redox homeostasis and discuss avenues for future research. Understanding the molecular mechanisms that link hypoxia-inducible factors to oxidative and reductive stresses is essential for comprehending several pathological conditions associated with hypoxia and redox imbalance.
氧化还原稳态，即氧化与还原过程之间的微妙平衡，对于细胞功能和整体机体健康至关重要。在分子水平上，细胞需要在活性氧（ROS）水平与诸如谷胱甘肽和烟酰胺腺嘌呤二核苷酸磷酸等还原当量之间保持精细平衡。由于ROS产生过多而导致的氧化还原稳态失衡会引发氧化应激，进而损害脂质、蛋白质和核酸。相反，由于还原当量过多而导致的细胞环境过度还原会导致还原应激，这也会干扰重要的细胞信号传导和生理过程。氧化还原稳态的破坏与多种病理状况相关，包括神经退行性疾病、炎症性疾病、癌症和心血管疾病。细胞采用多种机制来应对氧化还原失衡。由缺氧诱导因子介导的缺氧反应途径负责感知和抵御低氧水平，在维持氧化还原稳态中起着至关重要的作用。在本综述中，我们强调了缺氧诱导因子与氧化还原稳态之间复杂且多方面的相互作用，并讨论了未来的研究方向。了解将缺氧诱导因子与氧化应激和还原应激联系起来的分子机制对于理解与缺氧和氧化还原失衡相关的几种病理状况至关重要。
