title: Oxidative stress regulates the ubiquitin-proteasome system and immunoproteasome functioning in a mouse model of X-adrenoleukodystrophy.
abstract: Oxidative damage is a pivotal aetiopathogenic factor in X-linked adrenoleukodystrophy. This is a neurometabolic disease characterized by the accumulation of very-long-chain fatty acids owing to the loss of function of the peroxisomal transporter Abcd1. Here, we used the X-linked adrenoleukodystrophy mouse model and patient's fibroblasts to detect malfunctioning of the ubiquitin-proteasome system resulting from the accumulation of oxidatively modified proteins, some involved in bioenergetic metabolism. Furthermore, the immunoproteasome machinery appears upregulated in response to oxidative stress, in the absence of overt inflammation. i-Proteasomes are recruited to mitochondria when fibroblasts are exposed to an excess of very-long-chain fatty acids in response to oxidative stress. Antioxidant treatment regulates proteasome expression, prevents i-proteasome induction and translocation of i-proteasomes to mitochondria. Our findings support a key role of i-proteasomes in quality control in mitochondria during oxidative damage in X-linked adrenoleukodystrophy, and perhaps in other neurodegenerative conditions with similar pathogeneses.
authors: Neurometabolic Diseases Laboratory, Institute of Neuropathology, IDIBELL, Hospitalet de Llobregat, Barcelona, Spain.
authors: Nathalie
authors: N
authors: Launay
authors: Montserrat
authors: M
authors: Ruiz
authors: Stéphane
authors: S
authors: Fourcade
authors: Agatha
authors: A
authors: Schlüter
authors: Cristina
authors: C
authors: Guilera
authors: Isidre
authors: I
authors: Ferrer
authors: Erwin
authors: E
authors: Knecht
authors: Aurora
authors: A
authors: Pujol
mesh_terms: D000326:Adrenoleukodystrophy / Q000276:immunology / Q000378:metabolism* / Q000503:physiopathology; D000818:Animals; D004195:Disease Models, Animal; D005347:Fibroblasts / Q000378:metabolism; D006801:Humans; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D018384:Oxidative Stress / Q000502:physiology*; D046988:Proteasome Endopeptidase Complex / Q000276:immunology / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D025801:Ubiquitin / Q000276:immunology / Q000378:metabolism*
chemical_list: D025801:Ubiquitin; D046988:Proteasome Endopeptidase Complex