Perturbed mitochondria-ER contacts in live neurons that model the amyloid pathology of Alzheimer's disease
- Autores
- 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
- Año de publicación
- 2019
- Idioma
- inglés
- Tipo de recurso
- artículo
- Estado
- versión publicada
- Descripción
- 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.
Fil: Martino Adami, Pamela Victoria. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigaciones Bioquímicas de Buenos Aires. Fundación Instituto Leloir. Instituto de Investigaciones Bioquímicas de Buenos Aires; Argentina. Universitat zu Köln; Alemania
Fil: Nichtová, Zuzana. Thomas Jefferson University; Estados Unidos
Fil: Weaver, David B.. Thomas Jefferson University; Estados Unidos
Fil: Bartok, Adam. Thomas Jefferson University; Estados Unidos
Fil: Wisniewski, Thomas. University of New York; Estados Unidos
Fil: Jones, Drew R.. University of New York; Estados Unidos
Fil: Do Carmo, Sonia. Mcgill University; Canadá
Fil: Castaño, Eduardo Miguel. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigaciones Bioquímicas de Buenos Aires. Fundación Instituto Leloir. Instituto de Investigaciones Bioquímicas de Buenos Aires; Argentina
Fil: Cuello, Claudio A.. Mcgill University; Canadá
Fil: Hajnóczky, György. Thomas Jefferson University; Estados Unidos
Fil: Morelli, Laura. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigaciones Bioquímicas de Buenos Aires. Fundación Instituto Leloir. Instituto de Investigaciones Bioquímicas de Buenos Aires; Argentina - Materia
-
ALZHEIMER
AMYLOID β/βCTF
FRET
MERC
MITOCHONDRIAL LIPIDS
PRIMARY NEURONAL CULTURES
TRANSGENIC RATS - Nivel de accesibilidad
- acceso abierto
- Condiciones de uso
- https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
- Repositorio
.jpg)
- Institución
- Consejo Nacional de Investigaciones Científicas y Técnicas
- OAI Identificador
- oai:ri.conicet.gov.ar:11336/96782
Ver los metadatos del registro completo
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Perturbed mitochondria-ER contacts in live neurons that model the amyloid pathology of Alzheimer's diseaseMartino Adami, Pamela VictoriaNichtová, ZuzanaWeaver, David B.Bartok, AdamWisniewski, ThomasJones, Drew R.Do Carmo, SoniaCastaño, Eduardo MiguelCuello, Claudio A.Hajnóczky, GyörgyMorelli, LauraALZHEIMERAMYLOID β/βCTFFRETMERCMITOCHONDRIAL LIPIDSPRIMARY NEURONAL CULTURESTRANSGENIC RATShttps://purl.org/becyt/ford/1.6https://purl.org/becyt/ford/1The 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.Fil: Martino Adami, Pamela Victoria. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigaciones Bioquímicas de Buenos Aires. Fundación Instituto Leloir. Instituto de Investigaciones Bioquímicas de Buenos Aires; Argentina. Universitat zu Köln; AlemaniaFil: Nichtová, Zuzana. Thomas Jefferson University; Estados UnidosFil: Weaver, David B.. Thomas Jefferson University; Estados UnidosFil: Bartok, Adam. Thomas Jefferson University; Estados UnidosFil: Wisniewski, Thomas. University of New York; Estados UnidosFil: Jones, Drew R.. University of New York; Estados UnidosFil: Do Carmo, Sonia. Mcgill University; CanadáFil: Castaño, Eduardo Miguel. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigaciones Bioquímicas de Buenos Aires. Fundación Instituto Leloir. Instituto de Investigaciones Bioquímicas de Buenos Aires; ArgentinaFil: Cuello, Claudio A.. Mcgill University; CanadáFil: Hajnóczky, György. Thomas Jefferson University; Estados UnidosFil: Morelli, Laura. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigaciones Bioquímicas de Buenos Aires. Fundación Instituto Leloir. Instituto de Investigaciones Bioquímicas de Buenos Aires; ArgentinaCompany of Biologists2019-10info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/96782Martino 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; 10-20190021-9533CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/doi/10.1242/jcs.229906info:eu-repo/semantics/altIdentifier/url/https://jcs.biologists.org/content/132/20/jcs229906info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-sa/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-10-22T11:44:14Zoai:ri.conicet.gov.ar:11336/96782instacron:CONICETInstitucionalhttp://ri.conicet.gov.ar/Organismo científico-tecnológicoNo correspondehttp://ri.conicet.gov.ar/oai/requestdasensio@conicet.gov.ar; lcarlino@conicet.gov.arArgentinaNo correspondeNo correspondeNo correspondeopendoar:34982025-10-22 11:44:14.745CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse |
| dc.title.none.fl_str_mv |
Perturbed mitochondria-ER contacts in live neurons that model the amyloid pathology of Alzheimer's disease |
| title |
Perturbed mitochondria-ER contacts in live neurons that model the amyloid pathology of Alzheimer's disease |
| spellingShingle |
Perturbed mitochondria-ER contacts in live neurons that model the amyloid pathology of Alzheimer's disease Martino Adami, Pamela Victoria ALZHEIMER AMYLOID β/βCTF FRET MERC MITOCHONDRIAL LIPIDS PRIMARY NEURONAL CULTURES TRANSGENIC RATS |
| title_short |
Perturbed mitochondria-ER contacts in live neurons that model the amyloid pathology of Alzheimer's disease |
| title_full |
Perturbed mitochondria-ER contacts in live neurons that model the amyloid pathology of Alzheimer's disease |
| title_fullStr |
Perturbed mitochondria-ER contacts in live neurons that model the amyloid pathology of Alzheimer's disease |
| title_full_unstemmed |
Perturbed mitochondria-ER contacts in live neurons that model the amyloid pathology of Alzheimer's disease |
| title_sort |
Perturbed mitochondria-ER contacts in live neurons that model the amyloid pathology of Alzheimer's disease |
| dc.creator.none.fl_str_mv |
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 |
| author |
Martino Adami, Pamela Victoria |
| author_facet |
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 |
| author_role |
author |
| author2 |
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 |
| author2_role |
author author author author author author author author author author |
| dc.subject.none.fl_str_mv |
ALZHEIMER AMYLOID β/βCTF FRET MERC MITOCHONDRIAL LIPIDS PRIMARY NEURONAL CULTURES TRANSGENIC RATS |
| topic |
ALZHEIMER AMYLOID β/βCTF FRET MERC MITOCHONDRIAL LIPIDS PRIMARY NEURONAL CULTURES TRANSGENIC RATS |
| purl_subject.fl_str_mv |
https://purl.org/becyt/ford/1.6 https://purl.org/becyt/ford/1 |
| dc.description.none.fl_txt_mv |
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. Fil: Martino Adami, Pamela Victoria. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigaciones Bioquímicas de Buenos Aires. Fundación Instituto Leloir. Instituto de Investigaciones Bioquímicas de Buenos Aires; Argentina. Universitat zu Köln; Alemania Fil: Nichtová, Zuzana. Thomas Jefferson University; Estados Unidos Fil: Weaver, David B.. Thomas Jefferson University; Estados Unidos Fil: Bartok, Adam. Thomas Jefferson University; Estados Unidos Fil: Wisniewski, Thomas. University of New York; Estados Unidos Fil: Jones, Drew R.. University of New York; Estados Unidos Fil: Do Carmo, Sonia. Mcgill University; Canadá Fil: Castaño, Eduardo Miguel. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigaciones Bioquímicas de Buenos Aires. Fundación Instituto Leloir. Instituto de Investigaciones Bioquímicas de Buenos Aires; Argentina Fil: Cuello, Claudio A.. Mcgill University; Canadá Fil: Hajnóczky, György. Thomas Jefferson University; Estados Unidos Fil: Morelli, Laura. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigaciones Bioquímicas de Buenos Aires. Fundación Instituto Leloir. Instituto de Investigaciones Bioquímicas de Buenos Aires; Argentina |
| description |
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. |
| publishDate |
2019 |
| dc.date.none.fl_str_mv |
2019-10 |
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info:eu-repo/semantics/article info:eu-repo/semantics/publishedVersion http://purl.org/coar/resource_type/c_6501 info:ar-repo/semantics/articulo |
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article |
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publishedVersion |
| dc.identifier.none.fl_str_mv |
http://hdl.handle.net/11336/96782 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 0021-9533 CONICET Digital CONICET |
| url |
http://hdl.handle.net/11336/96782 |
| identifier_str_mv |
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 0021-9533 CONICET Digital CONICET |
| dc.language.none.fl_str_mv |
eng |
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eng |
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info:eu-repo/semantics/altIdentifier/doi/10.1242/jcs.229906 info:eu-repo/semantics/altIdentifier/url/https://jcs.biologists.org/content/132/20/jcs229906 |
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Company of Biologists |
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CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicas |
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dasensio@conicet.gov.ar; lcarlino@conicet.gov.ar |
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