2024-03-29T08:03:08Zhttp://digital.csic.es/dspace-oai/requestoai:digital.csic.es:10261/799392016-02-17T19:12:05Zcom_10261_22com_10261_1col_10261_275
Mitochondrial dysfunction associated with a mutation in the Notch3 gene in a CADASIL family
Bornstein, Belén
Fernández-Moreno, Miguel Ángel
Martín, Miguel A.
Campos, Yolanda
Arenas, Joaquín
Garesse, Rafael
[Background]: Cerebral autosomal arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is characterized by recurrent subcortical ischemic strokes and dementia caused by mutations in the Notch3 gene. In Drosophila melanogaster, Notch signaling has a pleiotropic effect, affecting most tissues of the organism during development. [Objective]: To characterize a potential mitochondrial dysfunction associated with mutations in the Notch3 gene. [Methods]: Biochemical, histochemical, molecular, and genetic analyses were performed on muscle biopsy specimens and fibroblasts obtained from patients of a Spanish family with CADASIL. Additional biochemical and molecular analyses of the N55e11 mutant of D. melanogaster were performed. [Results]: In muscle biopsy specimens, a significant decrease was found in the activity of complex I (NADH [reduced form of nicotinamide adenine dinucleotide] dehydrogenase), and in one patient, histochemical analysis showed the presence of ragged-red fibers with abnormal cytochrome c oxidase staining. Reduced fibroblast activity of complex V (ATP synthase) was found. Supporting data on patients with CADASIL, it was found that the mutation N55e11 in Drosophila decreases the activity of mitochondrial respiratory complexes I and V. [Conclusions]: Mitochondrial respiratory chain activity responds, directly or indirectly, to the Notch signaling pathway. Mitochondrial dysfunction in patients with CADASIL may be an epiphenomenon, but results of this study suggest that the pathophysiology of the disease could include a defect in oxidative phosphorylation.
Peer Reviewed
2013-07-19T10:34:54Z
2013-07-19T10:34:54Z
2001
2013-07-19T10:34:54Z
artículo
http://purl.org/coar/resource_type/c_6501
doi: 10.1212/WNL.57.7.1235
issn: 0028-3878
e-issn: 1526-632X
Neurology 57(7): 1235-1238 (2001)
http://hdl.handle.net/10261/79939
10.1212/WNL.57.7.1235
en
none
Lippincott Williams & Wilkins