Impaired autophagy: The collateral damage of lysosomal storage disorders
Lysosomal storage disorders (LSDs), which number over fifty, are monogenically inherited and caused by mutations in genes encoding proteins that are involved in lysosomal function. Lack of the functional protein results in storage of a distinctive material within the lysosomes, which for years was t...
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doaj-22b6d0ff621f461baa247fed12f7f8b42021-01-22T04:50:12ZengElsevierEBioMedicine2352-39642021-01-0163103166Impaired autophagy: The collateral damage of lysosomal storage disordersRachel Myerowitz0Rosa Puertollano1Nina Raben2Department of Biology St. Mary's College of Maryland, St. Mary's City Maryland, 20686, USACell and Developmental Biology Center, National Heart, Lung, and Blood Institute, NIH, 50 South Dr./Room 3533, Bethesda, MD 20892, USACell and Developmental Biology Center, National Heart, Lung, and Blood Institute, NIH, 50 South Dr./Room 3533, Bethesda, MD 20892, USA; Corresponding author.Lysosomal storage disorders (LSDs), which number over fifty, are monogenically inherited and caused by mutations in genes encoding proteins that are involved in lysosomal function. Lack of the functional protein results in storage of a distinctive material within the lysosomes, which for years was thought to determine the pathophysiology of the disorder. However, our current view posits that the primary storage material disrupts the normal role of the lysosome in the autophagic pathway resulting in the secondary storage of autophagic debris. It is this “collateral damage” which is common to the LSDs but nonetheless intricately nuanced in each. We have selected five LSDs resulting from defective proteins that govern widely different lysosomal functions including glycogen degradation (Pompe), lysosomal transport (Cystinosis), lysosomal trafficking (Danon), glycolipid degradation (Gaucher) and an unidentified function (Batten) and argue that despite the disparate functions, these proteins, when mutant, all impair the autophagic process uniquely.http://www.sciencedirect.com/science/article/pii/S2352396420305429LysosomeAutophagyGaucher diseaseBatten diseaseDanon diseasePompe disease |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Rachel Myerowitz Rosa Puertollano Nina Raben |
spellingShingle |
Rachel Myerowitz Rosa Puertollano Nina Raben Impaired autophagy: The collateral damage of lysosomal storage disorders EBioMedicine Lysosome Autophagy Gaucher disease Batten disease Danon disease Pompe disease |
author_facet |
Rachel Myerowitz Rosa Puertollano Nina Raben |
author_sort |
Rachel Myerowitz |
title |
Impaired autophagy: The collateral damage of lysosomal storage disorders |
title_short |
Impaired autophagy: The collateral damage of lysosomal storage disorders |
title_full |
Impaired autophagy: The collateral damage of lysosomal storage disorders |
title_fullStr |
Impaired autophagy: The collateral damage of lysosomal storage disorders |
title_full_unstemmed |
Impaired autophagy: The collateral damage of lysosomal storage disorders |
title_sort |
impaired autophagy: the collateral damage of lysosomal storage disorders |
publisher |
Elsevier |
series |
EBioMedicine |
issn |
2352-3964 |
publishDate |
2021-01-01 |
description |
Lysosomal storage disorders (LSDs), which number over fifty, are monogenically inherited and caused by mutations in genes encoding proteins that are involved in lysosomal function. Lack of the functional protein results in storage of a distinctive material within the lysosomes, which for years was thought to determine the pathophysiology of the disorder. However, our current view posits that the primary storage material disrupts the normal role of the lysosome in the autophagic pathway resulting in the secondary storage of autophagic debris. It is this “collateral damage” which is common to the LSDs but nonetheless intricately nuanced in each. We have selected five LSDs resulting from defective proteins that govern widely different lysosomal functions including glycogen degradation (Pompe), lysosomal transport (Cystinosis), lysosomal trafficking (Danon), glycolipid degradation (Gaucher) and an unidentified function (Batten) and argue that despite the disparate functions, these proteins, when mutant, all impair the autophagic process uniquely. |
topic |
Lysosome Autophagy Gaucher disease Batten disease Danon disease Pompe disease |
url |
http://www.sciencedirect.com/science/article/pii/S2352396420305429 |
work_keys_str_mv |
AT rachelmyerowitz impairedautophagythecollateraldamageoflysosomalstoragedisorders AT rosapuertollano impairedautophagythecollateraldamageoflysosomalstoragedisorders AT ninaraben impairedautophagythecollateraldamageoflysosomalstoragedisorders |
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