Artículo
Perturbed mitochondria-ER contacts in live neurons that model the amyloid pathology of Alzheimer's disease
Martino Adami, Pamela Victoria
; Nichtová, Zuzana; Weaver, David B.; Bartok, Adam; Wisniewski, Thomas; Jones, Drew R.; Do Carmo, Sonia; Castaño, Eduardo Miguel
; Cuello, Claudio A.; Hajnóczky, György; Morelli, Laura
Fecha de publicación:
10/2019
Editorial:
Company of Biologists
Revista:
Journal of Cell Science
ISSN:
0021-9533
Idioma:
Inglés
Tipo de recurso:
Artículo publicado
Clasificación temática:
Resumen
The use of fixed fibroblasts from familial and sporadic Alzheimer's disease patients has previously indicated an upregulation of mitochondria-ER contacts (MERCs) as a hallmark of Alzheimer's disease. Despite its potential significance, the relevance of these results is limited because they were not extended to live neurons. Here we performed a dynamic in vivo analysis of MERCs in hippocampal neurons from McGill-R-Thy1-APP transgenic rats, a model of Alzheimer's disease-like amyloid pathology. Live FRET imaging of neurons from transgenic rats revealed perturbed 'lipid-MERCs' (gap width <10 nm), while 'Ca2+-MERCs' (10-20 nm gap width) were unchanged. In situ TEM showed no significant differences in the lipid- MERCs:totalMERCs or lipid-MERCs:mitochondria ratios; however, the average length of lipid-MERCs was significantly decreased in neurons from transgenic rats as compared to controls. In accordance with FRET results, untargeted lipidomics showed significant decreases in levels of 12 lipids and bioenergetic analysis revealed respiratory dysfunction of mitochondria from transgenic rats. Thus, our results reveal changes in MERC structures coupled with impaired mitochondrial functions in Alzheimer's disease-related neurons. This article has an associated First Person interview with the first author of the paper.
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Articulos(IIBBA)
Articulos de INST.DE INVEST.BIOQUIMICAS DE BS.AS(I)
Articulos de INST.DE INVEST.BIOQUIMICAS DE BS.AS(I)
Citación
Martino Adami, Pamela Victoria; Nichtová, Zuzana; Weaver, David B.; Bartok, Adam; Wisniewski, Thomas; et al.; Perturbed mitochondria-ER contacts in live neurons that model the amyloid pathology of Alzheimer's disease; Company of Biologists; Journal of Cell Science; 132; 20; 10-2019
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