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Targeting Mitochondrial Network Architecture in Down Syndrome and Aging
Mitochondria are organelles that mainly control energy conversion in the cell. In addition, they also participate in many relevant activities, such as the regulation of apoptosis and calcium levels, and other metabolic tasks, all closely linked to cell viability. Functionality of mitochondria appear...
Autores principales: | , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2020
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7247689/ https://www.ncbi.nlm.nih.gov/pubmed/32365535 http://dx.doi.org/10.3390/ijms21093134 |
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author | Mollo, Nunzia Cicatiello, Rita Aurilia, Miriam Scognamiglio, Roberta Genesio, Rita Charalambous, Maria Paladino, Simona Conti, Anna Nitsch, Lucio Izzo, Antonella |
author_facet | Mollo, Nunzia Cicatiello, Rita Aurilia, Miriam Scognamiglio, Roberta Genesio, Rita Charalambous, Maria Paladino, Simona Conti, Anna Nitsch, Lucio Izzo, Antonella |
author_sort | Mollo, Nunzia |
collection | PubMed |
description | Mitochondria are organelles that mainly control energy conversion in the cell. In addition, they also participate in many relevant activities, such as the regulation of apoptosis and calcium levels, and other metabolic tasks, all closely linked to cell viability. Functionality of mitochondria appears to depend upon their network architecture that may dynamically pass from an interconnected structure with long tubular units, to a fragmented one with short separate fragments. A decline in mitochondrial quality, which presents itself as an altered structural organization and a function of mitochondria, has been observed in Down syndrome (DS), as well as in aging and in age-related pathologies. This review provides a basic overview of mitochondrial dynamics, from fission/fusion mechanisms to mitochondrial homeostasis. Molecular mechanisms determining the disruption of the mitochondrial phenotype in DS and aging are discussed. The impaired activity of the transcriptional co-activator PGC-1α/PPARGC1A and the hyperactivation of the mammalian target of rapamycin (mTOR) kinase are emerging as molecular underlying causes of these mitochondrial alterations. It is, therefore, likely that either stimulating the PGC-1α activity or inhibiting mTOR signaling could reverse mitochondrial dysfunction. Evidence is summarized suggesting that drugs targeting either these pathways or other factors affecting the mitochondrial network may represent therapeutic approaches to improve and/or prevent the effects of altered mitochondrial function. Overall, from all these studies it emerges that the implementation of such strategies may exert protective effects in DS and age-related diseases. |
format | Online Article Text |
id | pubmed-7247689 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-72476892020-06-10 Targeting Mitochondrial Network Architecture in Down Syndrome and Aging Mollo, Nunzia Cicatiello, Rita Aurilia, Miriam Scognamiglio, Roberta Genesio, Rita Charalambous, Maria Paladino, Simona Conti, Anna Nitsch, Lucio Izzo, Antonella Int J Mol Sci Review Mitochondria are organelles that mainly control energy conversion in the cell. In addition, they also participate in many relevant activities, such as the regulation of apoptosis and calcium levels, and other metabolic tasks, all closely linked to cell viability. Functionality of mitochondria appears to depend upon their network architecture that may dynamically pass from an interconnected structure with long tubular units, to a fragmented one with short separate fragments. A decline in mitochondrial quality, which presents itself as an altered structural organization and a function of mitochondria, has been observed in Down syndrome (DS), as well as in aging and in age-related pathologies. This review provides a basic overview of mitochondrial dynamics, from fission/fusion mechanisms to mitochondrial homeostasis. Molecular mechanisms determining the disruption of the mitochondrial phenotype in DS and aging are discussed. The impaired activity of the transcriptional co-activator PGC-1α/PPARGC1A and the hyperactivation of the mammalian target of rapamycin (mTOR) kinase are emerging as molecular underlying causes of these mitochondrial alterations. It is, therefore, likely that either stimulating the PGC-1α activity or inhibiting mTOR signaling could reverse mitochondrial dysfunction. Evidence is summarized suggesting that drugs targeting either these pathways or other factors affecting the mitochondrial network may represent therapeutic approaches to improve and/or prevent the effects of altered mitochondrial function. Overall, from all these studies it emerges that the implementation of such strategies may exert protective effects in DS and age-related diseases. MDPI 2020-04-29 /pmc/articles/PMC7247689/ /pubmed/32365535 http://dx.doi.org/10.3390/ijms21093134 Text en © 2020 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Review Mollo, Nunzia Cicatiello, Rita Aurilia, Miriam Scognamiglio, Roberta Genesio, Rita Charalambous, Maria Paladino, Simona Conti, Anna Nitsch, Lucio Izzo, Antonella Targeting Mitochondrial Network Architecture in Down Syndrome and Aging |
title | Targeting Mitochondrial Network Architecture in Down Syndrome and Aging |
title_full | Targeting Mitochondrial Network Architecture in Down Syndrome and Aging |
title_fullStr | Targeting Mitochondrial Network Architecture in Down Syndrome and Aging |
title_full_unstemmed | Targeting Mitochondrial Network Architecture in Down Syndrome and Aging |
title_short | Targeting Mitochondrial Network Architecture in Down Syndrome and Aging |
title_sort | targeting mitochondrial network architecture in down syndrome and aging |
topic | Review |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7247689/ https://www.ncbi.nlm.nih.gov/pubmed/32365535 http://dx.doi.org/10.3390/ijms21093134 |
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