Artículo de revista
The dopamine metabolite aminochrome inhibits mitochondrial complex i and modifies the expression of iron transporters DMT1 and FPN1
Fecha
2012Registro en:
BioMetals, Volumen 25, Issue 4, 2018, Pages 795-803
09660844
15728773
10.1007/s10534-012-9525-y
Autor
Aguirre, Pabla
Urrutia, Pamela J.
Tapia, Victoria
Villa, Monica
Paris Pizarro, Irmgard
Segura Aguilar, Juan
Núñez González, Marco
Institución
Resumen
Hallmarks of idiopathic and some forms of familial Parkinson's disease are mitochondrial dysfunction, iron accumulation and oxidative stress in dopaminergic neurons of the substantia nigra. There seems to be a causal link between these three conditions, since mitochondrial dysfunction can give rise to increased electron leak and reactive oxygen species production. In turn, recent evidence indicates that diminished activity of mitochondrial complex I results in decreased Fe-S cluster synthesis and anomalous activation of Iron Regulatory Protein 1. Thus, mitochondrial dysfunction could be a founding event in the process that leads to neuronal death. Here, we present evidence showing that at low micromolar concentrations, the dopamine metabolite aminochrome inhibits complex I and ATP production in SH-SY5Y neuroblastoma cells differentiated into a dopaminergic phenotype. This effect is apparently direct, since it is replicated in isolated mitochondria. Additionally, overnight treatment wit