The lysosomal membrane—export of metabolites and beyond

Abstract

Lysosomes are degradative organelles in eukaryotic cells mediating the hydrolytic catabolism of various macromolecules to small basic building blocks. These low molecular weight metabolites are transported across the lysosomal membrane and re-used in the cytoplasm and other organelles for biosynthetic pathways. Even though in the past 20 years our understanding of the Accepted Article This article is protected by copyright. All rights reserved lysosomal membrane regarding various transporters, other integral-and peripheral-membrane proteins, the lipid composition but also its turnover has greatly improved, there are still many unresolved questions concerning key aspects of the function of the lysosomal membrane. These include a possible function of lysosomes as a cellular storage compartment, yet unidentified transporters mediating the export e.g. of various amino acids, mechanisms mediating the transport of lysosomal membrane proteins from the Golgi apparatus to lysosomes, and the turnover of lysosomal membrane proteins. We here review the current knowledge about the lysosomal membrane and identify some of the open questions that need to be solved in the future for a comprehensive and complete understanding of how lysosomes communicate with other organelles, cellular processes, and pathways.

The lysosomal transporter TAPL has a dual role as peptide translocator and phosphatidylserine floppase

“…1 c–e, 4 a, and 6a ). This TAPL-mediated lipid redistribution suggests that TAPL is involved in regulating lipid trafficking between the inner and outer leaflets of lysosomal membranes, or between other organelles or intraluminal vesicles, and thus may contribute to the characteristic lipid composition of the lysosome 48 , 49 .…”

Current Methods to Unravel the Functional Properties of Lysosomal Ion Channels and Transporters

“…The major lysosomal membrane proteins are instead extensively Nglycosylated with oligosaccharide chains modified by Golgi enzymes. This "glycocalyx" is believed to protect the luminal loops of membrane proteins from degradation by lysosomal proteases [154]. In silico analysis of proteomes suggests that protection from vacuolar proteases has instead evolved by limiting the length of luminal domains of tonoplast proteins [153].…”

Engaging the Lysosome and Lysosome-Dependent Cell Death in Cancer

“…Given this diversity and the propensity for alterations during cancer, it is worth detailing a few key membrane constituents. For a more in-depth discussion, the reader is referred to several excellent topical reviews (108)(109)(110)(111)(112)(113).…”