Universität zu Köln

Martino Adami, Pamela, V, Nichtova, Zuzana, Weaver, David B., Bartok, Adam, Wisniewski, Thomas ORCID: 0000-0002-3379-8966, Jones, Drew R., Do Carmo, Sonia ORCID: 0000-0002-6152-8613, Castano, Eduardo M., Cuello, A. Claudio, Hajnoczky, Gyorgy and Morelli, Laura (2019). Perturbed mitochondria-ER contacts in live neurons that model the amyloid pathology of Alzheimer's disease. J. Cell Sci., 132 (20). CAMBRIDGE: COMPANY BIOLOGISTS LTD. ISSN 1477-9137

Full text not available from this repository.

Abstract

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:total MERCs 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 mitochondria! functions in Alzheimer's disease-related neurons. This article has an associated First Person interview with the first author of the paper.

Item Type:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code Martino Adami, Pamela, V UNSPECIFIED UNSPECIFIED UNSPECIFIED Nichtova, Zuzana UNSPECIFIED UNSPECIFIED UNSPECIFIED Weaver, David B. UNSPECIFIED UNSPECIFIED UNSPECIFIED Bartok, Adam UNSPECIFIED UNSPECIFIED UNSPECIFIED Wisniewski, Thomas UNSPECIFIED orcid.org/0000-0002-3379-8966 UNSPECIFIED Jones, Drew R. UNSPECIFIED UNSPECIFIED UNSPECIFIED Do Carmo, Sonia UNSPECIFIED orcid.org/0000-0002-6152-8613 UNSPECIFIED Castano, Eduardo M. UNSPECIFIED UNSPECIFIED UNSPECIFIED Cuello, A. Claudio UNSPECIFIED UNSPECIFIED UNSPECIFIED Hajnoczky, Gyorgy UNSPECIFIED UNSPECIFIED UNSPECIFIED Morelli, Laura UNSPECIFIED UNSPECIFIED UNSPECIFIED
URN:	urn:nbn:de:hbz:38-132043
DOI:	10.1242/jcs.229906
Journal or Publication Title:	J. Cell Sci.
Volume:	132
Number:	20
Date:	2019
Publisher:	COMPANY BIOLOGISTS LTD
Place of Publication:	CAMBRIDGE
ISSN:	1477-9137
Language:	English
Faculty:	Unspecified
Divisions:	Unspecified
Subjects:	no entry
Uncontrolled Keywords:	Keywords Language C-TERMINAL FRAGMENT; ENDOPLASMIC-RETICULUM; PRECURSOR PROTEIN; BETA-PEPTIDE; CALCIUM; METABOLISM; MEMBRANE; ACTIVATION; PHOSPHATIDYLETHANOLAMINE; BIOENERGETICS Multiple languages Cell Biology Multiple languages
Refereed:	Yes
URI:	http://kups.ub.uni-koeln.de/id/eprint/13204