Redox compartmentalization and cellular stress.
Redox compartmentalization and cellular stress.
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DOI：
10.1111/j.1463-1326.2010.01266.x
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发表时间：
2010-10
期刊：
影响因子：
--
通讯作者：
Go YM
中科院分区：
文献类型：
--
作者：
Jones DP;Go YM
哺乳动物细胞是高度组织化的，以优化功能。例如，线粒体中的氧化能量产生过程与质膜氧化还原信号复合体隔离，也与易受氧化剂诱导突变的核DNA隔离。蛋白质在大分子中是独一无二的，因为它具有可逆的可氧化元素，即支持结构和功能动态调节的“硫开关”。越来越多的证据表明，氧化还原信号和控制系统维持在动力学受限的稳态下，这些稳态高度偏离氧化还原平衡，并且细胞器之间存在明显的差异。在胁迫条件下，线粒体最还原，最容易氧化，而细胞核也在还原，但相对抵抗氧化。在隔室内，谷胱甘肽和硫氧还蛋白系统提供平行和非冗余的功能，以维持蛋白质半胱氨酸亚群的动态氧化还原平衡，这些亚群在氧化还原信号和控制中发挥作用。这种组织使细胞能够准备好应对细胞压力，但也创造了脆弱的场所。重要的是，氧化还原组织的破坏是疾病的常见基础。研究工具正在变得可用于阐明亚细胞氧化还原组织的细节，这一进展突显了新一代靶向抗氧化剂在疾病预防中增强和恢复氧化还原信号和控制的机会。
Mammalian cells are highly organized to optimize function. For instance, oxidative energy-producing processes in mitochondria are sequestered away from plasma membrane redox signaling complexes and also from nuclear DNA which is subject to oxidant-induced mutation. Proteins are unique among macromolecules in having reversible oxidizable elements, “sulfur switches”, which support dynamic regulation of structure and function. Accumulating evidence shows that redox signaling and control systems are maintained under kinetically limited steady-states which are highly displaced from redox equilibrium and distinct among organelles. Mitochondria are most reducing and susceptible to oxidation under stressed conditions while nuclei are also reducing but relatively resistant to oxidation. Within compartments, the glutathione and thioredoxin systems serve parallel and non-redundant functions to maintain the dynamic redox balance of subsets of protein cysteines which function in redox signaling and control. This organization allows cells to be poised to respond to cell stress but also creates sites of vulnerability. Importantly, disruption of redox organization is a common basis for disease. Research tools are becoming available to elucidate details of subcellular redox organization, and this development highlights an opportunity for a new generation of targeted antioxidants to enhance and restore redox signaling and control in disease prevention.
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影响因子：
5.8
作者：
CLARKE, ED;GOULDING, KH;WARDMAN, P
通讯作者：
WARDMAN, P
DOI：
10.1016/0006-291x(84)91629-2
发表时间：
1984-01-01
影响因子：
3.1
作者：
DEGROOT, H;NOLL, T
通讯作者：
NOLL, T
影响因子：
48
作者：
Gutscher, Marcus;Pauleau, Anne-Laure;Dick, Tobias P.
通讯作者：
Dick, Tobias P.
DOI：
10.1073/pnas.0509035102
发表时间：
2005-12-13
影响因子：
11.1
作者：
Austin, CD;Wen, XH;Scales, SJ
通讯作者：
Scales, SJ
影响因子：
3.8
作者：
Go, Young-Mi;Craige, Siobhan E.;Jones, Dean P.
通讯作者：
Jones, Dean P.