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Mitochondrial Dysfunction in Lysosomal Storage Disorders

Lysosomal storage diseases (LSDs) describe a heterogeneous group of rare inherited metabolic disorders that result from the absence or loss of function of lysosomal hydrolases or transporters, resulting in the progressive accumulation of undigested material in lysosomes. The accumulation of substanc...

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Autores principales: de la Mata, Mario, Cotán, David, Villanueva-Paz, Marina, de Lavera, Isabel, Álvarez-Córdoba, Mónica, Luzón-Hidalgo, Raquel, Suárez-Rivero, Juan M., Tiscornia, Gustavo, Oropesa-Ávila, Manuel
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2016
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5456326/
https://www.ncbi.nlm.nih.gov/pubmed/28933411
http://dx.doi.org/10.3390/diseases4040031
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author de la Mata, Mario
Cotán, David
Villanueva-Paz, Marina
de Lavera, Isabel
Álvarez-Córdoba, Mónica
Luzón-Hidalgo, Raquel
Suárez-Rivero, Juan M.
Tiscornia, Gustavo
Oropesa-Ávila, Manuel
author_facet de la Mata, Mario
Cotán, David
Villanueva-Paz, Marina
de Lavera, Isabel
Álvarez-Córdoba, Mónica
Luzón-Hidalgo, Raquel
Suárez-Rivero, Juan M.
Tiscornia, Gustavo
Oropesa-Ávila, Manuel
author_sort de la Mata, Mario
collection PubMed
description Lysosomal storage diseases (LSDs) describe a heterogeneous group of rare inherited metabolic disorders that result from the absence or loss of function of lysosomal hydrolases or transporters, resulting in the progressive accumulation of undigested material in lysosomes. The accumulation of substances affects the function of lysosomes and other organelles, resulting in secondary alterations such as impairment of autophagy, mitochondrial dysfunction, inflammation and apoptosis. LSDs frequently involve the central nervous system (CNS), where neuronal dysfunction or loss results in progressive neurodegeneration and premature death. Many LSDs exhibit signs of mitochondrial dysfunction, which include mitochondrial morphological changes, decreased mitochondrial membrane potential (ΔΨm), diminished ATP production and increased generation of reactive oxygen species (ROS). Furthermore, reduced autophagic flux may lead to the persistence of dysfunctional mitochondria. Gaucher disease (GD), the LSD with the highest prevalence, is caused by mutations in the GBA1 gene that results in defective and insufficient activity of the enzyme β-glucocerebrosidase (GCase). Decreased catalytic activity and/or instability of GCase leads to accumulation of glucosylceramide (GlcCer) and glucosylsphingosine (GlcSph) in the lysosomes of macrophage cells and visceral organs. Mitochondrial dysfunction has been reported to occur in numerous cellular and mouse models of GD. The aim of this manuscript is to review the current knowledge and implications of mitochondrial dysfunction in LSDs.
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spelling pubmed-54563262017-09-12 Mitochondrial Dysfunction in Lysosomal Storage Disorders de la Mata, Mario Cotán, David Villanueva-Paz, Marina de Lavera, Isabel Álvarez-Córdoba, Mónica Luzón-Hidalgo, Raquel Suárez-Rivero, Juan M. Tiscornia, Gustavo Oropesa-Ávila, Manuel Diseases Review Lysosomal storage diseases (LSDs) describe a heterogeneous group of rare inherited metabolic disorders that result from the absence or loss of function of lysosomal hydrolases or transporters, resulting in the progressive accumulation of undigested material in lysosomes. The accumulation of substances affects the function of lysosomes and other organelles, resulting in secondary alterations such as impairment of autophagy, mitochondrial dysfunction, inflammation and apoptosis. LSDs frequently involve the central nervous system (CNS), where neuronal dysfunction or loss results in progressive neurodegeneration and premature death. Many LSDs exhibit signs of mitochondrial dysfunction, which include mitochondrial morphological changes, decreased mitochondrial membrane potential (ΔΨm), diminished ATP production and increased generation of reactive oxygen species (ROS). Furthermore, reduced autophagic flux may lead to the persistence of dysfunctional mitochondria. Gaucher disease (GD), the LSD with the highest prevalence, is caused by mutations in the GBA1 gene that results in defective and insufficient activity of the enzyme β-glucocerebrosidase (GCase). Decreased catalytic activity and/or instability of GCase leads to accumulation of glucosylceramide (GlcCer) and glucosylsphingosine (GlcSph) in the lysosomes of macrophage cells and visceral organs. Mitochondrial dysfunction has been reported to occur in numerous cellular and mouse models of GD. The aim of this manuscript is to review the current knowledge and implications of mitochondrial dysfunction in LSDs. MDPI 2016-10-11 /pmc/articles/PMC5456326/ /pubmed/28933411 http://dx.doi.org/10.3390/diseases4040031 Text en © 2016 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
de la Mata, Mario
Cotán, David
Villanueva-Paz, Marina
de Lavera, Isabel
Álvarez-Córdoba, Mónica
Luzón-Hidalgo, Raquel
Suárez-Rivero, Juan M.
Tiscornia, Gustavo
Oropesa-Ávila, Manuel
Mitochondrial Dysfunction in Lysosomal Storage Disorders
title Mitochondrial Dysfunction in Lysosomal Storage Disorders
title_full Mitochondrial Dysfunction in Lysosomal Storage Disorders
title_fullStr Mitochondrial Dysfunction in Lysosomal Storage Disorders
title_full_unstemmed Mitochondrial Dysfunction in Lysosomal Storage Disorders
title_short Mitochondrial Dysfunction in Lysosomal Storage Disorders
title_sort mitochondrial dysfunction in lysosomal storage disorders
topic Review
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5456326/
https://www.ncbi.nlm.nih.gov/pubmed/28933411
http://dx.doi.org/10.3390/diseases4040031
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