Department of Microbiology & Immunology, Montana State University, Bozeman, Montana, USA.
Antioxid Redox Signal. 2020 Dec 1;33(16):1158-1173. doi: 10.1089/ars.2020.8151. Epub 2020 Aug 14.
In humans, imbalances in the reduction-oxidation (redox) status of cells are associated with many pathological states. In addition, many therapeutics and prophylactics used as interventions for diverse pathologies either directly modulate oxidant levels or otherwise influence endogenous cellular redox systems. The cellular machineries that maintain redox homeostasis or that function within antioxidant defense systems rely heavily on the regulated reactivities of sulfur atoms either within or derived from the amino acids cysteine and methionine. Recent advances have substantially advanced our understanding of the complex and essential chemistry of biological sulfur-containing molecules. The redox machineries that maintain cellular homeostasis under diverse stresses can consume large amounts of energy to generate reducing power and/or large amounts of sulfur-containing nutrients to replenish or sustain intracellular stores. By understanding the metabolic pathways underlying these responses, one can better predict how to protect cells from specific stresses. Here, we summarize the current state of knowledge about the impacts of different stresses on cellular metabolism of sulfur-containing molecules. This analysis suggests that there remains more to be learned about how cells use sulfur chemistry to respond to stresses, which could in turn lead to advances in therapeutic interventions for some exposures or conditions.
在人类中,细胞的氧化还原(redox)状态失衡与许多病理状态有关。此外,许多用于治疗和预防多种疾病的治疗药物和预防药物直接调节氧化剂水平,或者以其他方式影响内源性细胞氧化还原系统。维持氧化还原稳态或在抗氧化防御系统内发挥作用的细胞机制严重依赖于半胱氨酸和蛋氨酸的氨基酸内或衍生的硫原子的调节反应性。最近的进展极大地提高了我们对生物含硫分子复杂而重要的化学的理解。在各种应激下维持细胞内稳态的氧化还原机制可以消耗大量能量来产生还原力和/或大量含硫营养素来补充或维持细胞内储存。通过了解这些反应背后的代谢途径,人们可以更好地预测如何保护细胞免受特定应激的影响。在这里,我们总结了关于不同应激对含硫分子细胞代谢影响的最新知识状态。这一分析表明,关于细胞如何利用硫化学来应对应激,仍有更多需要了解,这反过来又可能导致在某些暴露或情况下的治疗干预方面取得进展。