Lysosomal thiol reductase negatively regulates autophagy by altering glutathione synthesis and oxidation

Chiang, Hao-Sen; Marić, Maja

doi:10.1016/j.freeradbiomed.2011.05.015

Cited by 66 publications

(50 citation statements)

References 87 publications

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“…GILT has been shown to alter cellular glutathione levels in murine fibroblasts, although glutathione is unlikely to be a major reducing equivalent in the endolysosomal system (12,56). Elucidating mechanisms by which GILT supports cathepsin S activity is a focus of ongoing research.…”

Section: Discussionmentioning

confidence: 99%

γ-Interferon-inducible Lysosomal Thiol Reductase (GILT) Maintains Phagosomal Proteolysis in Alternatively Activated Macrophages

Balce

Allan

McKenna

et al. 2014

Journal of Biological Chemistry

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Background: GILT is known to reduce disulfide bonds in endosomes, lysosomes, and phagosomes. Results: GILT, in addition to reducing disulfide bonds, maintains phagosomal proteolytic activity, particularly in alternatively activated macrophages. Conclusion: GILT maintains activity of cysteine proteases in phagosomes. Significance: These results reveal a novel role for GILT that may affect antigen processing and efficiency of hydrolysis of phagocytosed protein.

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Section: Discussionmentioning

confidence: 99%

γ-Interferon-inducible Lysosomal Thiol Reductase (GILT) Maintains Phagosomal Proteolysis in Alternatively Activated Macrophages

Balce

Allan

McKenna

et al. 2014

Journal of Biological Chemistry

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“…Loss of GILT in immune cells such as T cells and monocytes has diminished cytokine production following Ag exposure or LPS (Lackman and Cresswell, 2006; Rausch and Hastings, 2012). Interestingly, loss of GILT increases mitochondrial oxidative damage and cytosolic HMGB1 accumulation (Chiang and Maric, 2011), suggesting a potential role of GILT in the regulation of secretory lysosome-mediated HMGB1 release (Lackman et al, 2007). …”

Section: Hmgb1 Releasementioning

confidence: 99%

HMGB1 in health and disease

Kang

Chen

Zhang

et al. 2014

Molecular Aspects of Medicine

801

828

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Complex genetic and physiological variations as well as environmental factors that drive emergence of chromosomal instability, development of unscheduled cell death, skewed differentiation, and altered metabolism are central to the pathogenesis of human diseases and disorders. Understanding the molecular bases for these processes is important for the development of new diagnostic biomarkers, and for identifying new therapeutic targets. In 1973, a group of non-histone nuclear proteins with high electrophoretic mobility was discovered and termed High-Mobility Group (HMG) proteins. The HMG proteins include three superfamilies termed HMGB, HMGN, and HMGA. High-mobility group box 1 (HMGB1), the most abundant and well-studied HMG protein, senses and coordinates the cellular stress response and plays a critical role not only inside of the cell as a DNA chaperone, chromosome guardian, autophagy sustainer, and protector from apoptotic cell death, but also outside the cell as the prototypic damage associated molecular pattern molecule (DAMP). This DAMP, in conjunction with other factors, thus has cytokine, chemokine, and growth factor activity, orchestrating the inflammatory and immune response. All of these characteristics make HMGB1 a critical molecular target in multiple human diseases including infectious diseases, ischemia, immune disorders, neurodegenerative diseases, metabolic disorders, and cancer. Indeed, a number of emergent strategies have been used to inhibit HMGB1 expression, release, and activity in vitro and in vivo. These include antibodies, peptide inhbitiors, RNAi, anti-coagulants, endogenous hormones, various chemical compounds, HMGB1-receptor and signaling pathway inhibition, artificial DNAs, physical strategies including vagus nerve stimulation and other surgical approaches. Future work further investigating the details of HMGB1 localizationtion, structure, post-translational modification, and identifccation of additional partners will undoubtedly uncover additional secrets regarding HMGB1’s multiple functions.

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“…After endocytotic uptake, CuO-NPs will most likely be directed in intracellular vesicles to the lysosomal compartment. Lysosomes contain an acidic and reducing environment [94,95] which facilitates the liberation of copper ions from CuO-NPs [96]. In addition, these conditions will provide Cu ?…”

Section: Intracellular Trafficking and Storage Of Copper And Copper Omentioning

confidence: 99%

Handling of Copper and Copper Oxide Nanoparticles by Astrocytes

Bulcke

Dringen

2015

Neurochem Res

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Copper is an essential trace element for many important cellular functions. However, excess of copper can impair cellular functions by copper-induced oxidative stress. In brain, astrocytes are considered to play a prominent role in the copper homeostasis. In this short review we summarise the current knowledge on the molecular mechanisms which are involved in the handling of copper by astrocytes. Cultured astrocytes efficiently take up copper ions predominantly by the copper transporter Ctr1 and the divalent metal transporter DMT1. In addition, copper oxide nanoparticles are rapidly accumulated by astrocytes via endocytosis. Cultured astrocytes tolerate moderate increases in intracellular copper contents very well. However, if a given threshold of cellular copper content is exceeded after exposure to copper, accelerated production of reactive oxygen species and compromised cell viability are observed. Upon exposure to sub-toxic concentrations of copper ions or copper oxide nanoparticles, astrocytes increase their copper storage capacity by upregulating the cellular contents of glutathione and metallothioneins. In addition, cultured astrocytes have the capacity to export copper ions which is likely to involve the copper ATPase 7A. The ability of astrocytes to efficiently accumulate, store and export copper ions suggests that astrocytes have a key role in the distribution of copper in brain. Impairment of this astrocytic function may be involved in diseases which are connected with disturbances in brain copper metabolism.

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Lysosomal thiol reductase negatively regulates autophagy by altering glutathione synthesis and oxidation

Cited by 66 publications

References 87 publications

γ-Interferon-inducible Lysosomal Thiol Reductase (GILT) Maintains Phagosomal Proteolysis in Alternatively Activated Macrophages

γ-Interferon-inducible Lysosomal Thiol Reductase (GILT) Maintains Phagosomal Proteolysis in Alternatively Activated Macrophages

HMGB1 in health and disease

Handling of Copper and Copper Oxide Nanoparticles by Astrocytes

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