Bánhegyi Gábor, Benedetti Angelo, Margittai Eva, Marcolongo Paola, Fulceri Rosella, Németh Csilla E, Szarka András
Department of Medical Chemistry, Molecular Biology and Pathobiochemistry, Semmelweis University Budapest, Budapest, Hungary.
Department of Molecular and Developmental Medicine, University of Siena, Siena, Italy.
Biochim Biophys Acta. 2014 Sep;1843(9):1909-16. doi: 10.1016/j.bbamcr.2014.05.016. Epub 2014 Jun 4.
Beyond its general role as antioxidant, specific functions of ascorbate are compartmentalized within the eukaryotic cell. The list of organelle-specific functions of ascorbate has been recently expanded with the epigenetic role exerted as a cofactor for DNA and histone demethylases in the nucleus. Compartmentation necessitates the transport through intracellular membranes; members of the GLUT family and sodium-vitamin C cotransporters mediate the permeation of dehydroascorbic acid and ascorbate, respectively. Recent observations show that increased consumption and/or hindered entrance of ascorbate in/to a compartment results in pathological alterations partially resembling to scurvy, thus diseases of ascorbate compartmentation can exist. The review focuses on the reactions and transporters that can modulate ascorbate concentration and redox state in three compartments: endoplasmic reticulum, mitochondria and nucleus. By introducing the relevant experimental and clinical findings we make an attempt to coin the term of ascorbate compartmentation disease.
除了其作为抗氧化剂的一般作用外，抗坏血酸的特定功能在真核细胞内是分区进行的。最近，随着抗坏血酸在细胞核中作为DNA和组蛋白去甲基化酶的辅助因子所发挥的表观遗传作用，其细胞器特异性功能的清单得以扩展。分区需要通过细胞内膜进行运输；GLUT家族成员和钠-维生素C共转运蛋白分别介导脱氢抗坏血酸和抗坏血酸的渗透。最近的观察结果表明，抗坏血酸在一个隔室中的消耗增加和/或进入受阻会导致部分类似于坏血病的病理改变，因此可能存在抗坏血酸分区疾病。本综述重点关注可调节内质网、线粒体和细胞核这三个隔室中抗坏血酸浓度和氧化还原状态的反应和转运蛋白。通过介绍相关的实验和临床发现，我们试图创造“抗坏血酸分区疾病”这一术语。
