Autophagy in lysosomal storage disorders

Andrew P. Lieberman, Rosa Puertollano, Nina Raben, Susan Slaugenhaupt, Steven U. Walkley, Andrea Ballabio

Research output: Contribution to journalReview article

206 Scopus citations

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."

Original languageEnglish (US)
Pages (from-to)719-730
Number of pages12
JournalAutophagy
Volume8
Issue number5
DOIs
StatePublished - May 2012

Keywords

  • Autophagy
  • Glycogenosis
  • Lysosomal storage disorders
  • Lysosomes
  • Mucolipidosis type IV
  • Mucopolysaccharidoses
  • Sphingolipidoses

ASJC Scopus subject areas

  • Molecular Biology
  • Cell Biology

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  • Cite this

    Lieberman, A. P., Puertollano, R., Raben, N., Slaugenhaupt, S., Walkley, S. U., & Ballabio, A. (2012). Autophagy in lysosomal storage disorders. Autophagy, 8(5), 719-730. https://doi.org/10.4161/auto.19469