Autophagy in lysosomal storage disorders
Open Access
- 13 May 2012
- journal article
- review article
- Published by Taylor & Francis Ltd in Autophagy
- Vol. 8 (5), 719-730
- https://doi.org/10.4161/auto.19469
Abstract
Lysosomes are ubiquitous intracellular organelles that have an acidic internal pH, and play crucial roles in cellular clearance. Numerous functions depend on normal lysosomes, including the turnover of cellular constituents, cholesterol homeostasis, downregulation of surface receptors, inactivation of pathogenic organisms, repair of the plasma membrane and bone remodeling. Lysosomal storage disorders (LSDs) are characterized by progressive accumulation of undigested macromolecules within the cell due to lysosomal dysfunction. As a consequence, many tissues and organ systems are affected, including brain, viscera, bone and cartilage. The progressive nature of phenotype development is one of the hallmarks of LSDs. In recent years biochemical and cell biology studies of LSDs have revealed an ample spectrum of abnormalities in a variety of cellular functions. These include defects in signaling pathways, calcium homeostasis, lipid biosynthesis and degradation and intracellular trafficking. Lysosomes also play a fundamental role in the autophagic pathway by fusing with autophagosomes and digesting their content. Considering the highly integrated function of lysosomes and autophagosomes it was reasonable to expect that lysosomal storage in LSDs would have an impact upon autophagy. The goal of this review is to provide readers with an overview of recent findings that have been obtained through analysis of the autophagic pathway in several types of LSDs, supporting the idea that LSDs could be seen primarily as “autophagy disorders.”Keywords
This publication has 119 references indexed in Scilit:
- Autophagy and mitochondria in Pompe disease: Nothing is so new as what has long been forgottenSeminars in Medical Genetics, Part C of the American Journal of Medical Genetics, 2012
- Transcriptional Activation of Lysosomal Exocytosis Promotes Cellular ClearanceDevelopmental Cell, 2011
- Endosomal/Lysosomal Processing of Gangliosides Affects Neuronal Cholesterol Sequestration in Niemann-Pick Disease Type CThe American Journal of Pathology, 2011
- Gaucher Disease Glucocerebrosidase and α-Synuclein Form a Bidirectional Pathogenic Loop in SynucleinopathiesCell, 2011
- Lysosomal Proteolysis and Autophagy Require Presenilin 1 and Are Disrupted by Alzheimer-Related PS1 MutationsCell, 2010
- Methods in Mammalian Autophagy ResearchCell, 2010
- Mucolipins: Intracellular TRPML1‐3 channelsFEBS Letters, 2010
- Structure of N-Terminal Domain of NPC1 Reveals Distinct Subdomains for Binding and Transfer of CholesterolCell, 2009
- Pathogenic cascades in lysosomal disease—Why so complex?Journal of Inherited Metabolic Disease, 2009
- Ubiquitin-dependent sorting of integral membrane proteins for degradation in lysosomesCurrent Opinion in Cell Biology, 2007