title: Lysosomotropic agents: impact on lysosomal membrane permeabilization and cell death.
abstract: Lysosomes are acidic organelles essential for degradation, signalling and cell homoeostasis. In addition, they play a key role in cell death. Permeabilization of the lysosomal membrane and release of hydrolytic enzymes to the cytosol accompanies apoptosis signalling in several systems. The regulatory mechanism of lysosomal stability is, however, poorly understood. Lipophilic or amphiphilic compounds with a basic moiety will become protonated and trapped within lysosomes, and such lysosomotropic behaviour is also found in many pharmacological drugs. The natural sphingolipid sphingosine exhibits lysosomotropic detergent ability and is an endogenous candidate for controlling lysosomal membrane permeabilization. The lysosomotropic properties of certain detergents might be of use in lysosome-targeting anticancer drugs and drug delivery system in the future. The present review summarizes the current knowledge on the targeting and permeabilizing properties of lysosomotropic detergents from a cellular and physicochemical perspective.
authors.affiliation: *Division of Cell Biology, Department of Clinical and Experimental Medicine, Faculty of Health Sciences, Linköping University, Pathology Clinic, County Council of Östergötland, S-58158 Linköping, Sweden.
authors.forename: Ana M
authors.initials: AM
authors.lastname: Villamil Giraldo
authors.affiliation: †Division of Chemistry, Department of Physics, Chemistry and Biology, Linköping University, S-58183 Linköping, Sweden.
authors.forename: Hanna
authors.initials: H
authors.lastname: Appelqvist
authors.affiliation: ‡Division of Molecular Physics, Department of Physics, Chemistry and Biology, Linköping University, S-58183 Linköping, Sweden.
authors.forename: Thomas
authors.initials: T
authors.lastname: Ederth
authors.affiliation: *Division of Cell Biology, Department of Clinical and Experimental Medicine, Faculty of Health Sciences, Linköping University, Pathology Clinic, County Council of Östergötland, S-58158 Linköping, Sweden.
authors.forename: Karin
authors.initials: K
authors.lastname: Öllinger
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects*; D055598:Chemical Phenomena; D003902:Detergents / Q000494:pharmacology; D016503:Drug Delivery Systems; D006801:Humans; D007425:Intracellular Membranes / Q000737:chemistry / Q000187:drug effects*; D008051:Lipid Bilayers / Q000737:chemistry; D008247:Lysosomes / Q000737:chemistry / Q000187:drug effects*; D049990:Membrane Transport Modulators / Q000494:pharmacology*; D010539:Permeability / Q000187:drug effects; D013110:Sphingosine / Q000494:pharmacology
chemical_list: D000970:Antineoplastic Agents; D003902:Detergents; D008051:Lipid Bilayers; D049990:Membrane Transport Modulators; D013110:Sphingosine