Cargando…
Forcing contacts between mitochondria and the endoplasmic reticulum extends lifespan in a Drosophila model of Alzheimer's disease
Eukaryotic cells are complex systems containing internal compartments with specialised functions. Among these compartments, the endoplasmic reticulum (ER) plays a major role in processing proteins for modification and delivery to other organelles, whereas mitochondria generate energy in the form of...
Autores principales: | , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
The Company of Biologists Ltd
2020
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6994956/ https://www.ncbi.nlm.nih.gov/pubmed/31822473 http://dx.doi.org/10.1242/bio.047530 |
_version_ | 1783493292163334144 |
---|---|
author | Garrido-Maraver, Juan Loh, Samantha H. Y. Martins, L. Miguel |
author_facet | Garrido-Maraver, Juan Loh, Samantha H. Y. Martins, L. Miguel |
author_sort | Garrido-Maraver, Juan |
collection | PubMed |
description | Eukaryotic cells are complex systems containing internal compartments with specialised functions. Among these compartments, the endoplasmic reticulum (ER) plays a major role in processing proteins for modification and delivery to other organelles, whereas mitochondria generate energy in the form of ATP. Mitochondria and the ER form physical interactions, defined as mitochondria–ER contact sites (MERCs) to exchange metabolites such as calcium ions (Ca(2+)) and lipids. Sites of contact between mitochondria and the ER can regulate biological processes such as ATP generation and mitochondrial division. The interactions between mitochondria and the ER are dynamic and respond to the metabolic state of cells. Changes in MERCs have been linked to metabolic pathologies such as diabetes, neurodegenerative diseases and sleep disruption. Here we explored the consequences of increasing contacts between mitochondria and the ER in flies using a synthetic linker. We showed that enhancing MERCs increases locomotion and extends lifespan. We also showed that, in a Drosophila model of Alzheimer's disease linked to toxic amyloid beta (Aβ), linker expression can suppress motor impairment and extend lifespan. We conclude that strategies for increasing contacts between mitochondria and the ER may improve symptoms of diseases associated with mitochondria dysfunction. A video abstract for this article is available at https://youtu.be/_YWA4oKZkes. This article has an associated First Person interview with the first author of the paper. |
format | Online Article Text |
id | pubmed-6994956 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | The Company of Biologists Ltd |
record_format | MEDLINE/PubMed |
spelling | pubmed-69949562020-02-03 Forcing contacts between mitochondria and the endoplasmic reticulum extends lifespan in a Drosophila model of Alzheimer's disease Garrido-Maraver, Juan Loh, Samantha H. Y. Martins, L. Miguel Biol Open Research Article Eukaryotic cells are complex systems containing internal compartments with specialised functions. Among these compartments, the endoplasmic reticulum (ER) plays a major role in processing proteins for modification and delivery to other organelles, whereas mitochondria generate energy in the form of ATP. Mitochondria and the ER form physical interactions, defined as mitochondria–ER contact sites (MERCs) to exchange metabolites such as calcium ions (Ca(2+)) and lipids. Sites of contact between mitochondria and the ER can regulate biological processes such as ATP generation and mitochondrial division. The interactions between mitochondria and the ER are dynamic and respond to the metabolic state of cells. Changes in MERCs have been linked to metabolic pathologies such as diabetes, neurodegenerative diseases and sleep disruption. Here we explored the consequences of increasing contacts between mitochondria and the ER in flies using a synthetic linker. We showed that enhancing MERCs increases locomotion and extends lifespan. We also showed that, in a Drosophila model of Alzheimer's disease linked to toxic amyloid beta (Aβ), linker expression can suppress motor impairment and extend lifespan. We conclude that strategies for increasing contacts between mitochondria and the ER may improve symptoms of diseases associated with mitochondria dysfunction. A video abstract for this article is available at https://youtu.be/_YWA4oKZkes. This article has an associated First Person interview with the first author of the paper. The Company of Biologists Ltd 2020-01-14 /pmc/articles/PMC6994956/ /pubmed/31822473 http://dx.doi.org/10.1242/bio.047530 Text en © 2020. Published by The Company of Biologists Ltd http://creativecommons.org/licenses/by/4.0This is an Open Access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution and reproduction in any medium provided that the original work is properly attributed. |
spellingShingle | Research Article Garrido-Maraver, Juan Loh, Samantha H. Y. Martins, L. Miguel Forcing contacts between mitochondria and the endoplasmic reticulum extends lifespan in a Drosophila model of Alzheimer's disease |
title | Forcing contacts between mitochondria and the endoplasmic reticulum extends lifespan in a Drosophila model of Alzheimer's disease |
title_full | Forcing contacts between mitochondria and the endoplasmic reticulum extends lifespan in a Drosophila model of Alzheimer's disease |
title_fullStr | Forcing contacts between mitochondria and the endoplasmic reticulum extends lifespan in a Drosophila model of Alzheimer's disease |
title_full_unstemmed | Forcing contacts between mitochondria and the endoplasmic reticulum extends lifespan in a Drosophila model of Alzheimer's disease |
title_short | Forcing contacts between mitochondria and the endoplasmic reticulum extends lifespan in a Drosophila model of Alzheimer's disease |
title_sort | forcing contacts between mitochondria and the endoplasmic reticulum extends lifespan in a drosophila model of alzheimer's disease |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6994956/ https://www.ncbi.nlm.nih.gov/pubmed/31822473 http://dx.doi.org/10.1242/bio.047530 |
work_keys_str_mv | AT garridomaraverjuan forcingcontactsbetweenmitochondriaandtheendoplasmicreticulumextendslifespaninadrosophilamodelofalzheimersdisease AT lohsamanthahy forcingcontactsbetweenmitochondriaandtheendoplasmicreticulumextendslifespaninadrosophilamodelofalzheimersdisease AT martinslmiguel forcingcontactsbetweenmitochondriaandtheendoplasmicreticulumextendslifespaninadrosophilamodelofalzheimersdisease |