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Lysosomal enzyme trafficking: from molecular mechanisms to human diseases

Braulke, Thomas, Carette, Jan E., Palm, Wilhelm·2024·Trends in Cell Biology
DOI 10.1016/j.tcb.2023.06.005
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Abstract

Lysosomes degrade and recycle macromolecules that are delivered through the biosynthetic, endocytic, and autophagic routes. Hydrolysis of the different classes of macromolecules is catalyzed by about 70 soluble enzymes that are transported from the Golgi apparatus to lysosomes in a mannose 6-phosphate (M6P)-dependent process. The molecular machinery that generates M6P tags for receptor-mediated targeting of lysosomal enzymes was thought to be understood in detail. However, recent studies on the M6P pathway have identified a previously uncharacterized core component, yielded structural insights in known components, and uncovered functions in various human diseases. Here we review molecular mechanisms of lysosomal enzyme trafficking and discuss its relevance for rare lysosomal disorders, cancer, and viral infection.

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  • CIMPR is a key receptor that traffics lysosomal enzymes from the TGN to the lysosomes.

    “The CIMPR is a key receptor that traffics lysosomal enzymes from the TGN to the lysosomes (Braulke and Bonifacino 2009; Braulke et al. 2023).”

    From The Alzheimer's Disease Gene SORL1 Regulates Lysosome Function in Human Microglia (2025) · cites this paper as Braulke et al. 2023

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Metadata

Authors
Braulke, T., Carette, J. E., & Palm, W.
ORCID
Venue
Trends in Cell Biology
Publisher
Elsevier BV
Published
2024-03
Volume
34
Issue
3
Pages
198-210
ISSN
0962-8924
DOI
10.1016/j.tcb.2023.06.005
Cited by
76
References
11
Language
en
Licence
Funders
Deutsche Forschungsgemeinschaft (CRC877, FOR2625 TP7, PA 3679/3-1)

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