The lysosome: from waste bag to potential therapeutic target
Open accessAbstract
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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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 measuredMicroglia 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
- Publisher
- Oxford University Press (OUP)
- 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
- bronze
- doi.org
- 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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