Cited by 772Autophagy in Disease and TherapyCellular transport and secretionCalcium signaling and nucleotide metabolism

The lysosome: from waste bag to potential therapeutic target

Open access
Appelqvist, Hanna, Wäster, Petra, Kågedal, Katarina, Öllinger, Karin·2013·Journal of Molecular Cell Biology

Abstract

Lysosomes are ubiquitous membrane-bound intracellular organelles with an acidic interior. They are central for degradation and recycling of macromolecules delivered by endocytosis, phagocytosis, and autophagy. In contrast to the rather simplified view of lysosomes as waste bags, nowadays lysosomes are recognized as advanced organelles involved in many cellular processes and are considered crucial regulators of cell homeostasis. The function of lysosomes is critically dependent on soluble lysosomal hydrolases (e.g. cathepsins) as well as lysosomal membrane proteins (e.g. lysosome-associated membrane proteins). This review focuses on lysosomal involvement in digestion of intra- and extracellular material, plasma membrane repair, cholesterol homeostasis, and cell death. Regulation of lysosomal biogenesis and function via the transcription factor EB (TFEB) will also be discussed. In addition, lysosomal contribution to diseases, including lysosomal storage disorders, neurodegenerative disorders, cancer, and cardiovascular diseases, is presented.

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Crossref · 10.1093/jmcb/mjt022

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  • Insufficient degradation of protein aggregates and chronic inflammation are driving forces of AD and PD brain pathology.

    “Growing evidence indicates that insufficient degradation of protein aggregates and chronic inflammation are driving forces of AD and PD brain pathology [30–32].”

    From Crosstalk between astrocytes and microglia results in increased degradation of α-synuclein and amyloid-β aggregates (2021) · cites this paper as [32]

    The Neurodegenerative disorders section links defective autophagy and lysosomal dysfunction to neurodegeneration and says brain inflammation is observed in Alzheimer’s and Parkinson’s diseases. The Future targeting section also links impaired lysosomal degradation to protein-accumulation diseases. But the paper describes inflammation as a secondary pathological change and hedges the role of lysosomal disturbance; it does not establish that chronic inflammation and insufficient aggregate degradation are both driving forces of AD and PD pathology. (LLM, conf=0.86)

    Experimental — accuracy not yet measured
  • Microglia in distinct basal ganglia nuclei differ in phagocytotic activity or metabolic state.

    “Together, these observations suggest that microglia in distinct BG nuclei differ in their phagocytotic activity or metabolic state (Appelqvist et al., 2013).”

    From Local cues establish and maintain region-specific phenotypes of basal ganglia microglia (2017) · cites this paper as Appelqvist et al., 2013

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Authors
Appelqvist, H., Wäster, P., Kågedal, K., & Öllinger, K.
Affiliations
Linköping University (SE)
Corresponding author
Öllinger, Karin
Venue
Journal of Molecular Cell Biology
Published
2013-08
Volume
5
Issue
4
Pages
214-226
ISSN
  • 1674-2788 (ISSN-L)
  • 1759-4685
OpenAlex
W2152462290
Cited by
772
References
201
Citations by year
2026: 34 · 2025: 43 · 2024: 49 · 2023: 47 · 2022: 59 · 2021: 71 · 2020: 64 · 2019: 72 · 2018: 75 · 2017: 97 · 2016: 71 · 2015: 57 · 2014: 30 · 2013: 3
FWCI
6.36
Type
journal article
Language
en
Open access
Locations
  • Journal of Molecular Cell Biology (publishedVersion)
  • PubMed (publishedVersion)
  • HighWire Press Open Archive (submittedVersion)
Funders
  • Cancerfonden
  • Vetenskapsrådet
Topics
  • Health Sciences › Medicine › Epidemiology › Autophagy in Disease and Therapy
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Cellular transport and secretion
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Physiology › Calcium signaling and nucleotide metabolism
Keywords
lysosomes, lysosomal enzymes, cathepsins, lysosomal membrane proteins, lysosome-associated membrane protein, autophagy, endocytosis, phagocytosis, macromolecule degradation, plasma membrane repair, cholesterol homeostasis, cell death, lysosomal biogenesis, TFEB, lysosomal storage disease, neurodegenerative diseases, cancer, cardiovascular disease
MeSH terms
Cell Membrane, Endocytosis, Homeostasis, Humans, Lysosomes, Models, Biological, Proteins, Lysosomal Storage Diseases, Apoptosis

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