title: Subcellular compartmentation of ascorbate and its variation in disease states.
abstract: 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.
authors.affiliation: Department of Medical Chemistry, Molecular Biology and Pathobiochemistry, Semmelweis University Budapest, Budapest, Hungary. Electronic address: banhegyi@eok.sote.hu.
authors.forename: Gábor
authors.initials: G
authors.lastname: Bánhegyi
authors.affiliation: Department of Molecular and Developmental Medicine, University of Siena, Siena, Italy.
authors.forename: Angelo
authors.initials: A
authors.lastname: Benedetti
authors.affiliation: Institute of Human Physiology and Clinical Experimental Research, Semmelweis University, Budapest, Hungary.
authors.forename: Eva
authors.initials: E
authors.lastname: Margittai
authors.affiliation: Department of Molecular and Developmental Medicine, University of Siena, Siena, Italy.
authors.forename: Paola
authors.initials: P
authors.lastname: Marcolongo
authors.affiliation: Department of Molecular and Developmental Medicine, University of Siena, Siena, Italy.
authors.forename: Rosella
authors.initials: R
authors.lastname: Fulceri
authors.affiliation: Department of Medical Chemistry, Molecular Biology and Pathobiochemistry, Semmelweis University Budapest, Budapest, Hungary.
authors.forename: Csilla E
authors.initials: CE
authors.lastname: Németh
authors.affiliation: Pathobiochemistry Research Group of Hungarian Academy of Sciences, Budapest, Hungary; Department of Applied Biotechnology and Food Science, Laboratory of Biochemistry and Molecular Biology, Budapest University of Technology and Economics, Budapest, Hungary.
authors.forename: András
authors.initials: A
authors.lastname: Szarka
mesh_terms: D000818:Animals; D001205:Ascorbic Acid / Q000378:metabolism*; D002451:Cell Compartmentation; D004194:Disease; D005786:Gene Expression Regulation; D006801:Humans; D008954:Models, Biological; D015388:Organelles / Q000378:metabolism
chemical_list: D001205:Ascorbic Acid
keywords: Arterial tortuosity syndrome; Ascorbate; Compartmentation; Dehydroascorbic acid; GLUT; Scurvy