title: Impairment of methyl cycle affects mitochondrial methyl availability and glutathione level in Down's syndrome.
abstract: In Down's syndrome there is evidence that increased gene expression coding for specific cystathionine beta-synthase translates directly into biochemical aberrations, which result in a biochemical and metabolic imbalance of the methyl status. This event is destined to impact mitochondrial function since methylation is a necessary event in mitochondria and relies on the availability and uptake of the methyl donor S-adenosylmethionine. Indeed mitochondrial dysfunctions have been widely described in Down's syndrome, but they have never been correlated to a possible mitochondrial methyl unbalance. In the present study we find that the mitochondrial levels of S-adenosylmethionine are reduced in Down's syndrome compared to control cells demonstrating the effect of the methyl unbalance on mitochondria. The possible role of methylation in mitochondria is discussed and some preliminary results on a possible methylation target are presented.
authors.affiliation: Department of Chemistry, University of Basilicata, 85100 Potenza, Italy.
authors.forename: Vittoria
authors.initials: V
authors.lastname: Infantino
authors.forename: Alessandra
authors.initials: A
authors.lastname: Castegna
authors.forename: Francesco
authors.initials: F
authors.lastname: Iacobazzi
authors.forename: Iolanda
authors.initials: I
authors.lastname: Spera
authors.forename: Iris
authors.initials: I
authors.lastname: Scala
authors.forename: Generoso
authors.initials: G
authors.lastname: Andria
authors.forename: Vito
authors.initials: V
authors.lastname: Iacobazzi
mesh_terms: D000293:Adolescent; D002352:Carrier Proteins / Q000235:genetics; D002461:Cell Line, Transformed; D002648:Child; D002675:Child, Preschool; D003600:Cytosol / Q000378:metabolism; D004314:Down Syndrome / Q000235:genetics / Q000378:metabolism / Q000503:physiopathology*; D005978:Glutathione / Q000378:metabolism*; D006801:Humans; D007223:Infant; D008745:Methylation; D008928:Mitochondria / Q000235:genetics / Q000378:metabolism*; D012436:S-Adenosylmethionine / Q000378:metabolism
chemical_list: D002352:Carrier Proteins; D012436:S-Adenosylmethionine; D005978:Glutathione