Lipid compartmentalization in the endosome system

Hullin-Matsuda, Françoise; Taguchi, Tomohiko; Greimel, Peter; Kobayashi, Toshihide

doi:10.1016/j.semcdb.2014.04.010

Cited by 81 publications

(82 citation statements)

References 123 publications

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“…Next, we studied the sn-positional isomers, diacylglycerophosphoglycerol (PG) and bis(monoacylglycero)phosphate (BMP), which are indistinguishable by LC-MS/MS (Figure 2b). Differentiating PGs and BMPs is essential since both are present in mammalian tissues but each has a different biological role and cellular location [27]. BMPs play an important role in endosomal pathways and differ from all animal phospholipids since they have two glycerol groups and an atypical sn -1-glycerophospho- sn -1′-glycerol ( sn 1: sn 1′) backbone configuration.…”

Section: Resultsmentioning

confidence: 99%

Uncovering biologically significant lipid isomers with liquid chromatography, ion mobility spectrometry and mass spectrometry

Kyle

Zhang

Weitz

et al. 2016

Analyst

206

203

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Understanding how biological molecules are generated, metabolized and eliminated in living systems is important for interpreting processes such as immune response and disease pathology. While genomic and proteomic studies have provided vast amounts of information over the last several decades, interest in lipidomics has also grown due to improved analytical technologies revealing altered lipid metabolism in type 2 diabetes, cancer, and lipid storage disease. Mass spectrometry (MS) measurements are currently the dominant approach for characterizing the lipidome by providing detailed information on the spatial and temporal composition of lipids. However, interpreting lipids’ biological roles is challenging due to the existence of numerous structural and stereoisomers (i.e. distinct acyl chain and double-bond positions), which are often unresolvable using present approaches. Here we show that combining liquid chromatography (LC) and structurally-based ion mobility spectrometry (IMS) measurement with MS analyses distinguishes lipid isomers and allows insight into biological and disease processes.

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Section: Resultsmentioning

confidence: 99%

Uncovering biologically significant lipid isomers with liquid chromatography, ion mobility spectrometry and mass spectrometry

Kyle

Zhang

Weitz

et al. 2016

Analyst

206

203

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“…25 Since the pH decreases along the endocytic pathway from the early endosome (pH 6) via the late endosome (pH 5.0) to the lysosome (pH 4.5), we have chosen to study the effect of the most acidic pH on the penetration potential and stability of our CPP/pDNA complexes. 15 …”

Section: Resultsmentioning

confidence: 99%

Effect of Lipid Headgroup Charge and pH on the Stability and Membrane Insertion Potential of Calcium Condensed Gene Complexes

et al. 2015

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Noncovalently condensed complexes of genetic material, cell penetrating peptides (CPPs), and calcium chloride present a nonviral route to improve transfection efficiency of nucleic acids (e.g., pDNA and siRNA). However, the exact mechanisms of membrane insertion and delivery of macromolecule complexes to intracellular locations as well as their stability in the intracellular environment are not understood. We show that calcium condensed gene complexes containing different hydrophilic (i.e., dTAT, K9, R9, and RH9) and amphiphilic (i.e., RA9, RL9, and RW9) CPPs formed stable cationic complexes of hydrodynamic radii 100 nm at neutral pH. However, increasing the acidity caused the complexes to become neutral or anionic and increase in size. Using zwitterionic and anionic phospholipid monolayers as models that mimic the membrane composition of the outer leaflet of cell membranes and intracellular vesicles and pHs that mimic the intracellular environment, we study the membrane insertion potential of these seven gene complexes (CPP/pDNA/Ca2+ complexes) into model membranes. At neutral pH, all gene complexes demonstrated the highest insertion potential into anionic phospholipid membranes, with complexes containing amphiphilic peptides showing the maximum insertion. However, at acidic pH, the gene complexes demonstrated maximum monolayer insertion into zwitterionic lipids, irrespective of the chemical composition of the CPP in the complexes. Our results suggest that in the neutral environment the complexes are unable to penetrate the zwitterionic lipid membranes but can penetrate through the anionic lipid membranes. However, the acidic pH mimicking the local environment in the late endosomes leads to a significant increase in adsorption of the complexes to zwitterionic lipid headgroups and decreases for anionic headgroups. These membrane–gene complex interactions may be responsible for the ability of the complexes to efficiently enter the intracellular environment through endocytosis and escape from the endosomes to effectively deliver their genetic payload.

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“…This process is triggered by acidic activation of proteolytic digestive enzymes primarily in phagocytic cells such as monocytes and macrophages (Hullin-Matsuda et al 2014). Autophagosomes possess a double-membrane that fuses with lysosomes to form an autolysosome, which facilitates the breakdown of encapsulated materials that subsequently may be employed for cell survival (Suzuki et al 2016).…”

Section: Particle-induced Lysosomal Membrane Permeability (Lmp)mentioning

confidence: 99%

Engineered nanomaterial-induced lysosomal membrane permeabilization and anti-cathepsin agents

Bunderson-Schelvan

Holian

Hamilton

2017

Journal of Toxicology and Environmental Health, Part B

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Engineered nanomaterials (ENMs), or small anthropogenic particles approximately < 100 nm in size and of various shapes and compositions, are increasingly incorporated into commercial products and used for industrial and medical purposes. There is an exposure risk to both the population at large and individuals in the workplace with inhalation exposures to ENMs being a primary concern. Further, there is increasing evidence to suggest that certain ENMs may represent a significant health risk, and many of these ENMs exhibit distinct similarities with other particles and fibers that are known to induce adverse health effects, such as asbestos, silica, and particulate matter (PM). Evidence regarding the importance of lysosomal membrane permeabilization (LMP) and release of cathepsins in ENM toxicity has been accumulating. The aim of this review was to describe our current understanding of the mechanisms leading to ENM-associated pathologies, including LMP and the role of cathepsins with a focus on inflammation. In addition, anti-cathepsin agents, some of which have been tested in clinical trials and may prove useful for ameliorating the harmful effects of ENM exposure are examined.

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Lipid compartmentalization in the endosome system

Cited by 81 publications

References 123 publications

Uncovering biologically significant lipid isomers with liquid chromatography, ion mobility spectrometry and mass spectrometry

Uncovering biologically significant lipid isomers with liquid chromatography, ion mobility spectrometry and mass spectrometry

Effect of Lipid Headgroup Charge and pH on the Stability and Membrane Insertion Potential of Calcium Condensed Gene Complexes

Engineered nanomaterial-induced lysosomal membrane permeabilization and anti-cathepsin agents

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