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...
Main Authors: | , , , , , , , , |
---|---|
Format: | Article |
Language: | English |
Published: |
MDPI AG
2016-10-01
|
Series: | Diseases |
Subjects: | |
Online Access: | http://www.mdpi.com/2079-9721/4/4/31 |
id |
doaj-20b6fa3b4efa4c2481fe0c40ff46662e |
---|---|
record_format |
Article |
spelling |
doaj-20b6fa3b4efa4c2481fe0c40ff46662e2020-11-25T00:16:09ZengMDPI AGDiseases2079-97212016-10-01443110.3390/diseases4040031diseases4040031Mitochondrial Dysfunction in Lysosomal Storage DisordersMario de la Mata0David Cotán1Marina Villanueva-Paz2Isabel de Lavera3Mónica Álvarez-Córdoba4Raquel Luzón-Hidalgo5Juan M. Suárez-Rivero6Gustavo Tiscornia7Manuel Oropesa-Ávila8Centro Andaluz de Biología del Desarrollo (CABD-CSIC-Universidad Pablo de Olavide), Sevilla 41013, SpainCentro Andaluz de Biología del Desarrollo (CABD-CSIC-Universidad Pablo de Olavide), Sevilla 41013, SpainCentro Andaluz de Biología del Desarrollo (CABD-CSIC-Universidad Pablo de Olavide), Sevilla 41013, SpainCentro Andaluz de Biología del Desarrollo (CABD-CSIC-Universidad Pablo de Olavide), Sevilla 41013, SpainCentro Andaluz de Biología del Desarrollo (CABD-CSIC-Universidad Pablo de Olavide), Sevilla 41013, SpainCentro Andaluz de Biología del Desarrollo (CABD-CSIC-Universidad Pablo de Olavide), Sevilla 41013, SpainCentro Andaluz de Biología del Desarrollo (CABD-CSIC-Universidad Pablo de Olavide), Sevilla 41013, SpainDepartment of Biomedical Sciences and Medicine, University of Algarve, Faro 8005-139, PortugalCentro Andaluz de Biología del Desarrollo (CABD-CSIC-Universidad Pablo de Olavide), Sevilla 41013, SpainLysosomal 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.http://www.mdpi.com/2079-9721/4/4/31lysosomal storage disordersmitochondrial dysfunctionGaucher disease |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Mario de la Mata David Cotán Marina Villanueva-Paz Isabel de Lavera Mónica Álvarez-Córdoba Raquel Luzón-Hidalgo Juan M. Suárez-Rivero Gustavo Tiscornia Manuel Oropesa-Ávila |
spellingShingle |
Mario de la Mata David Cotán Marina Villanueva-Paz Isabel de Lavera Mónica Álvarez-Córdoba Raquel Luzón-Hidalgo Juan M. Suárez-Rivero Gustavo Tiscornia Manuel Oropesa-Ávila Mitochondrial Dysfunction in Lysosomal Storage Disorders Diseases lysosomal storage disorders mitochondrial dysfunction Gaucher disease |
author_facet |
Mario de la Mata David Cotán Marina Villanueva-Paz Isabel de Lavera Mónica Álvarez-Córdoba Raquel Luzón-Hidalgo Juan M. Suárez-Rivero Gustavo Tiscornia Manuel Oropesa-Ávila |
author_sort |
Mario de la Mata |
title |
Mitochondrial Dysfunction in Lysosomal Storage Disorders |
title_short |
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_sort |
mitochondrial dysfunction in lysosomal storage disorders |
publisher |
MDPI AG |
series |
Diseases |
issn |
2079-9721 |
publishDate |
2016-10-01 |
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. |
topic |
lysosomal storage disorders mitochondrial dysfunction Gaucher disease |
url |
http://www.mdpi.com/2079-9721/4/4/31 |
work_keys_str_mv |
AT mariodelamata mitochondrialdysfunctioninlysosomalstoragedisorders AT davidcotan mitochondrialdysfunctioninlysosomalstoragedisorders AT marinavillanuevapaz mitochondrialdysfunctioninlysosomalstoragedisorders AT isabeldelavera mitochondrialdysfunctioninlysosomalstoragedisorders AT monicaalvarezcordoba mitochondrialdysfunctioninlysosomalstoragedisorders AT raquelluzonhidalgo mitochondrialdysfunctioninlysosomalstoragedisorders AT juanmsuarezrivero mitochondrialdysfunctioninlysosomalstoragedisorders AT gustavotiscornia mitochondrialdysfunctioninlysosomalstoragedisorders AT manueloropesaavila mitochondrialdysfunctioninlysosomalstoragedisorders |
_version_ |
1725384195930324992 |